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Evaluation of the neurotoxic effects of chronic embryonic exposure with inorganic mercury on motor and anxiety-like responses in zebrafish (Danio rerio) larvae

Abu Bakar N, Mohd Sata NS, Ramlan NF, Wan Ibrahim WN, Zulkifli SZ, Che Abdullah CA, et al.

Neurotoxicol Teratol, 2017 Jan-Feb;59:53-61.
PMID: 27919701 DOI: 10.1016/j.ntt.2016.11.008

Chronic exposure to mercury (Hg) can lead to cumulative impairments in motor and cognitive functions including alteration in anxiety responses. Although several risk factors have been identified in recent year, little is known about the environmental factors that either due exposure toward low level of inorganic mercury that may led to the developmental disorders. The present study investigated the effects of embryonic exposure of mercury chloride on motor function and anxiety-like behavior. The embryo exposed to 6 different concentrations of HgCl2 (7.5, 15, 30, 100, 125, 250nM) at 5hpf until hatching (72hpf) in a semi-static condition. The mortality rate increased in a dose dependent manner where the chronic embryonic exposure to 100nM decreased the number of tail coiling, heartbeat, and swimming activity. Aversive stimulus was used to examine the effects of 100nM interferes with the development of anxiety-related behavior. No elevation in both thigmotaxis and avoidance response of 6dpf larvae exposed with 100nM were found. Biochemical analysis showed HgCl2 exposure affects proteins, lipids, carbohydrates and nucleic acids of the zebrafish larvae. These results showed that implication of HgCl2 on locomotor and biochemical defects affects motor performance and anxiety-like responses. Yet, the potential underlying mechanisms these responses need to be further investigated which is crucial to prevent potential hazards on the developing organism due to neurotoxicant exposure.

Matched MeSH terms: Heart Rate/drug effects
Fulltext Spread of spinal anaesthesia with 0.5% bupivacaine: influence of the vertebral interspace and speed of injection

Chin KW, Chin NM, Chin MK

Med J Malaysia, 1994 Jun;49(2):142-8.
PMID: 8090093

Three millilitres of plain 0.5% bupivacaine were injected intrathecally at two different spinal interspaces (L2/3 and L4/5) and at two different speeds (15 and 30 sec) in four groups of ten patients. Injection at L2/3 over 15 sec produced a significantly higher mean maximum spread of analgesia (T6.4) when compared to injection at L4-5 over 15 sec (T10.3) (P < 0.05). Over the same interspace L2/3, injection over 15 sec also produced a higher level of spread as compared to the 30 sec group (p < 0.05). At 15 min there was a greater fall in blood pressure in the L2/3 15 sec group when compared to the other groups (p < 0.01). There was a further decrease in the blood pressure in L2/3 15 sec and L4/5 30 sec groups after 30 minutes of blockade (p < 0.01). Therefore close monitoring of cardiovascular parameters must be continued for at least 30 min in spinal anaesthesia with bupivacaine.

Matched MeSH terms: Heart Rate/drug effects
Cardiovascular effects in the rat of dihydrocorynantheine isolated from Uncaria callophylla

Chang P, Koh YK, Geh SL, Soepadmo E, Goh SH, Wong AK

J Ethnopharmacol, 1989 Apr;25(2):213-5.
PMID: 2747255
Matched MeSH terms: Heart Rate/drug effects
Toxicity of the venom of the sea-snake, Laticauda colubrina, with observations on a Malay "folk cure"

Levey HA

Toxicon, 1969 May;6(4):269-76.
PMID: 5805121
Matched MeSH terms: Heart Rate/drug effects
Comparison of the effects of butorphanol-midazolam-medetomidine and butorphanol-azaperone-medetomidine in wild common palm civets (Paradoxurus musangus)

Ahmad AA, Douay G, Low MR, Fabbri S, Chen HC

Vet Anaesth Analg, 2021 May;48(3):380-387.
PMID: 33827780 DOI: 10.1016/j.vaa.2021.02.003

OBJECTIVE: To assess the efficacy of butorphanol-azaperone-medetomidine (BAM) and butorphanol-midazolam-medetomidine (BMM) protocols for immobilization of wild common palm civets (Paradoxurus musangus) with subsequent antagonization with atipamezole.
STUDY DESIGN: Prospective, randomized, blinded clinical trial.
ANIMALS: A total of 40 adult wild common palm civets, 24 female and 16 male, weighing 1.5-3.4 kg.
METHODS: The civets were randomly assigned for anesthesia with butorphanol, azaperone and medetomidine (0.6, 0.6 and 0.2 mg kg-1, respectively; group BAM) or with butorphanol, midazolam and medetomidine (0.3, 0.4 and 0.1 mg kg-1, respectively; group BMM) intramuscularly (IM) in a squeeze cage. When adequately relaxed, the trachea was intubated for oxygen administration. Physiological variables were recorded every 5 minutes after intubation. Following morphometric measurements, sampling, microchipping and parasite treatment, medetomidine was reversed with atipamezole at 1.0 or 0.5 mg kg-1 IM to groups BAM and BMM, respectively. Physiological variables and times to reach the different stages of anesthesia were compared between groups.
RESULTS: Onset time of sedation and recumbency was similar in both groups; time to achieve complete relaxation and tracheal intubation was longer in group BAM. Supplementation with isoflurane was required to enable intubation in five civets in group BAM and one civet in group BMM. All civets in group BAM required topical lidocaine to facilitate intubation. End-tidal carbon dioxide partial pressure was lower in group BAM, but heart rate, respiratory rate, rectal temperature, peripheral hemoglobin oxygen saturation and mean arterial blood pressure were not different. All civets in both groups recovered well following administration of atipamezole.
CONCLUSIONS AND CLINICAL RELEVANCE: Both BAM and BMM combinations were effective for immobilizing wild common palm civets. The BMM combination had the advantage of producing complete relaxation that allowed intubation more rapidly.

Matched MeSH terms: Heart Rate/drug effects
Effect of glyphosate-based herbicide on early life stages of Java medaka (Oryzias javanicus): a potential tropical test fish

Yusof S, Ismail A, Alias MS

Mar Pollut Bull, 2014 Aug 30;85(2):494-8.
PMID: 24731878 DOI: 10.1016/j.marpolbul.2014.03.022

Glyphosate is globally a widely used herbicide, yet there is little information on their toxicity to marine fishes. Java medaka, a small tropical fish native to coastal areas in several Southeast Asian countries, is viewed as a suitable candidate for toxicity test and thus was used for this study. Java medaka adults were cultured in the laboratory and the fertilized eggs of the F2 generation were exposed to different concentrations of glyphosate-based herbicide (100, 200, 300, 400 and 500 ppm) until they hatched. The survival and hatching rates of the embryos, changes in the heart rate and morphological impairments were recorded. Generally, survival and hatching percentage decreased as glyphosate concentration increased. Absence of pectoral fin(s) and cornea, permanently bent tail, irregular shaped abdomen, and cell disruption in the fin, head and abdomen are among the common teratogenic effects observed. Furthermore, risk factor also increased with the increased in glyphosate concentrations.

Matched MeSH terms: Heart Rate/drug effects
Method optimization to assess endothelial function in females-duration of glyceryl trinitrate effect

Ibrahim NN, Rasool AH, Wong AR, Rahman AR

Methods Find Exp Clin Pharmacol, 2007 Jun;29(5):349-52.
PMID: 17805437

Pulse-wave analysis (PWA) combined with pharmacological challenges has recently been used as a method to measure endothelial function. This involved administration of glyceryl trinitrate (GTN), followed by salbutamol as endothelium-independent and -dependent vasodilators, respectively. The duration of GTN effect needs to be established before the administration of salbutamol. Baseline augmentation index (AIx) and pulse-wave velocity (PWV) measurements were taken in 11 healthy female subjects (mean age 23.27 +/- 3.66 years). Sublingual GTN 0.5 mg was administered for 3 min, followed by AIx and PWV measurements every 5 min till 20 min and then every 10 min until 40 min post-GTN. Maximum change in AIx post-GTN was at 3 min with a mean change from the baseline of -17.86% +/- 4.40% (p < 0.001). There were no significant changes noted after 30 and 40 min with mean change being -0.82% +/- 2.61% and 0.14% +/- 3.20%, respectively (p > 0.05). Significant changes in PWV were noted at 5 and 10 min with the mean change of -0.33 +/- 0.36 m/s and -0.33 +/- 0.35 m/s, respectively (p = 0.01). There were no further changes noted at 15 min and thereafter (p > 0.05). A duration of at least 30 min after GTN is required for AIx and PWV values to reach their baseline. Thus, the administration of salbutamol should be given only after 30 min of sublingual GTN for the assessment of endothelial function.

Matched MeSH terms: Heart Rate/drug effects
Development of a zebrafish model for toxicity evaluation of adulterated Apis mellifera honey

Fakhlaei R, Selamat J, Abdull Razis AF, Sukor R, Ahmad S, Khatib A, et al.

Chemosphere, 2024 May;356:141736.
PMID: 38554873 DOI: 10.1016/j.chemosphere.2024.141736

Since ancient times, honey has been used for medical purposes and the treatment of various disorders. As a high-quality food product, the honey industry is prone to fraud and adulteration. Moreover, limited experimental studies have investigated the impact of adulterated honey consumption using zebrafish as the animal model. The aims of this study were: (1) to calculate the lethal concentration (LC50) of acid-adulterated Apis mellifera honey on embryos, (2) to investigate the effect of pure and acid-adulterated A. mellifera honey on hatching rate (%) and heart rate of zebrafish (embryos and larvae), (3) to elucidate toxicology of selected adulterated honey based on lethal dose (LD50) using adult zebrafish and (4) to screen the metabolites profile of adulterated honey from blood serum of adult zebrafish. The result indicated the LC50 of 31.10 ± 1.63 (mg/ml) for pure A. mellifera honey, while acetic acid demonstrates the lowest LC50 (4.98 ± 0.06 mg/ml) among acid adulterants with the highest mortality rate at 96 hpf. The treatment of zebrafish embryos with adulterated A. mellifera honey significantly (p ≤ 0.05) increased the hatching rate (%) and decreased the heartbeat rate. Acute, prolong-acute, and sub-acute toxicology tests on adult zebrafish were conducted at a concentration of 7% w/w of acid adulterants. Furthermore, the blood serum metabolite profile of adulterated-honey-treated zebrafish was screened by LC-MS/MS analysis and three endogenous metabolites have been revealed: (1) Xanthotoxol or 8-Hydroxypsoralen, (2) 16-Oxoandrostenediol, and (3) 3,5-Dicaffeoyl-4-succinoylquinic acid. These results prove that employed honey adulterants cause mortality that contributes to higher toxicity. Moreover, this study introduces the zebrafish toxicity test as a new promising standard technique for the potential toxicity assessment of acid-adulterated honey in this study and hazardous food adulterants for future studies.

Matched MeSH terms: Heart Rate/drug effects
Protective effects of pyridoxine, amlodipine, and their combination in a vasopressin-induced angina model in rats

Al-Khawlani MA, Al-Madhagi WM, Sabati AM, ALomaisi SAMA, Al-Najar M

Naunyn Schmiedebergs Arch Pharmacol, 2025 Aug;398(8):10983-10995.
PMID: 40067440 DOI: 10.1007/s00210-025-03905-6

Vitamin B6 (pyridoxine) vitamins are of interest in preventative and protective strategies in cardiovascular disease. However, the safety and efficacy of vitamin B6 has been questioned. The aim of this study was to study the protective effect of pyridoxine, amlodipine, and their combination against vasopressin-induced angina model in rats. The administration of vasopressin (1 IU/kg, i.v.) to the rats elevated the S-wave level of the electrocardiogram reflecting the presence of subendocardial ischemia, whereas it decreased of the heart rate, resulting in the increase of the cardiac enzymes, creatine kinase MB (CK MB), and lactate dehydrogenase (LDH). In the vasopressin-induced angina model, oral administration of pyridoxine in dose of 5, 7, 10 mg/kg revealed dose-dependent suppression of vasopressin-triggered of ST elevation and in reduced of heart rat. In addition, pyridoxine produced dose-dependent suppression of cardiac enzymes, creatine kinase MB (CK MB), and lactate dehydrogenase (LDH) more than amlodipine and isosorbide; while in contrast, the combination of pyridoxine with amlodipine resulted in a trend towards increased adverse cardiovascular events; pyridoxine in dose 7 mg/kg was found to be more potent than pyridoxine in doses 5, 10 mg/kg, amlodipine and isosorbide on vasopressin-induced angina in rats. Pyridoxine in dose of (5, 7 mg) prevents cardiac necrosis and artery well thickened on vasopressin-induced angina modal. Pyridoxine's protective effects may be mediated by improved endothelial nitric oxide synthase (eNOS) function, reduction of homocysteine levels, and modulation of sympathetic activity. Pyridoxine at optimal doses shows promise as a novel therapeutic agent for coronary heart disease prevention, warranting further investigation into its potential clinical applications.

Matched MeSH terms: Heart Rate/drug effects
Fulltext Chemical immobilization of free-ranging and captive Sunda clouded leopards (Neofelis diardi) with two anesthetic protocols: medetomidine-ketamine and tiletamine-zolazepam

Nájera F, Hearn AJ, Ross J, Ramírez Saldivar DA, Evans MN, Guerrero-Sánchez S, et al.

J Vet Med Sci, 2017 Nov 17;79(11):1892-1898.
PMID: 28904261 DOI: 10.1292/jvms.17-0259

There is currently no available information regarding the veterinary management of Sunda clouded leopards (Neofelis diardi), either in captivity or in the wild. In this study, 12 Sunda clouded leopards were anesthetized between January 2008 and February 2014 for medical exams, and/or GPS-collaring. Seven wild-caught individuals were kept in captivity and 5 free-ranging animals were captured by cage traps. Two anesthesia combinations were used: medetomidine-ketamine (M-K) or tiletamine-zolazepam (T-Z). Atipamezole (0.2 mg/kg im) was used as an antagonist for medetomidine. Medetomidine (range: 0.039-0.054 mg/kg) and ketamine (range: 3-4.39 mg/kg) were administered during 5 immobilizations, resulting in median induction times of 7 min. After a median anesthesia time of 56 min, atipamezole was injected, observing effects of antagonism at a median time of 12 min. T-Z (range: 6.8-10.8 mg/kg) was administered on 7 occasions. Median induction times observed with this combination were shorter than with M-K (4 min vs 7 min; P=0.04), and anesthesia and recovery times were significantly longer (244 and 35 min vs 56 and 16 min, respectively; P=0.02). Lower heart rates were measured in the M-K group, while lower rectal temperatures were found in the T-Z group. Both combinations resulted in safe and reliable immobilizations, although given the favorable anesthesia and recovery times of M-K, we recommend this approach over T-Z for the veterinary handling of Sunda clouded leopards.

Matched MeSH terms: Heart Rate/drug effects
Evaluation of anaesthetic and cardiorespiratory effects after intramuscular administration of alfaxalone alone, alfaxalone-ketamine and alfaxalone-butorphanol-medetomidine in common marmosets (Callithrix jacchus)

Miyabe-Nishiwaki T, Miwa M, Konoike N, Kaneko A, Ishigami A, Natsume T, et al.

J Med Primatol, 2020 12;49(6):291-299.
PMID: 32654222 DOI: 10.1111/jmp.12482

BACKGROUND: Anaesthesia is often required in common marmosets undergoing various procedures. The aim of this study was to evaluate anaesthetic and cardiopulmonary effects of alfaxalone, alfaxalone-ketamine and alfaxalone-butorphanol-medetomidine in common marmosets.
METHODS: The following treatments were repeatedly administered to seven female common marmosets: Treatment A, alfaxalone (12 mg kg-1 ) alone; treatment AK, alfaxalone (1 mg animal-1 ) plus ketamine (2.5 mg animal-1 ); treatment AMB, alfaxalone (4 mg kg-1 ), medetomidine (50 µg kg-1 ) plus butorphanol (0.3 mg kg-1 ); and treatment AMB-Ati, AMB with atipamezole at 45 minutes.
RESULTS AND CONCLUSIONS: Marmosets became laterally recumbent and unresponsive for approximately 30 minutes in A and AK and for approximately 60 minutes in AMB. The animals showed rapid recovery following atipamezole injection in AMB-Ati. The decrease in heart rate and SpO2 was significantly greater in AMB compared to A and AK. Oxygen supplementation, anaesthetic monitors and atipamezole should be available especially when AMB is administered.

Matched MeSH terms: Heart Rate/drug effects
Fulltext Fetal supraventricular tachycardia--a case report

Soh EBS, Raman S, Chia PMK

Med J Malaysia, 1998 Sep;53(3):280-3.
PMID: 10968167

A gravid patient with fetal supraventricular tachycardia is presented. A review of this rare condition and the present recommended mode of therapy are discussed.

Matched MeSH terms: Heart Rate/drug effects
Cardiovascular effects of aspidofractinine-type alkaloids from Kopsia

Mok SL, Yoganathan K, Lim TM, Kam TS

J Nat Prod, 1998 Mar;61(3):328-32.
PMID: 9544563

Intravenous injection of the aspidofractinine alkaloid, kopsingine (1, 0.2-10.0 mg/kg) from Kopsia teoi, produced dose-related decreases in the mean arterial blood pressure and heart rate in anesthetized spontaneously hypertensive rats, which were similar to those seen in normotensive controls. Minor modifications in the molecular structure of kopsingine, as in kopsaporine (2, the 12-demethoxy derivative of kopsingine) and 14,15-dihydrokopsingine (4), did not significantly alter the hypotensive responses, whereas a more drastic change in the structure, as in the heptacyclic kopsidine A (3) and the 3-to-17 oxo-bridged compound 5, resulted in an increase in blood pressure. The antihypertensive effects of kopsingine (1) and its congeners (2 and 4) along with the pressor effects produced by the heptacyclic oxo-bridged compounds (5 and 3) could be ascribed to central as well as peripheral actions.

Matched MeSH terms: Heart Rate/drug effects
Suppression of hypotensive responses of captopril and enalapril by the kallikrein inhibitor aprotinin in spontaneously hypertensive rats

Sharma JN, Amrah SS, Noor AR

Pharmacology, 1995 Jun;50(6):363-9.
PMID: 7568335

The present investigation evaluated the effects of aprotinin, an inhibitor of kallikrein, on blood pressure responses, heart rate, and duration of hypotension induced by acute administration of captopril and enalapril (angiotensin-converting enzyme inhibitors) in anaesthetized spontaneously hypertensive rats. Captopril (20 mg/kg) and enalapril (20 mg/kg) administered intravenously caused a significant (p < 0.001) fall in systolic and diastolic blood pressures in the absence of aprotinin. In contrast, captopril (20 mg/kg) and enalapril (20 mg/kg) failed (p > 0.05) to cause a fall in systolic and diastolic blood pressures in the presence of aprotinin (2 mg/kg). Captopril and enalapril were able to significantly reduce the heart rate (p < 0.05 and p < 0.001) in the presence as well as in the absence of aprotinin. The duration of hypotension produced by captopril and enalapril was abolished significantly (p < 0.001) in the presence of aprotinin. These findings may suggest that captopril and enalapril caused hypotension via the kallikrein pathway, since the kallikrein inhibitor aprotinin can antagonize the hypotensive responses of these agents. Thus, kallikrein may be an independent mediator in the regulation of blood pressure.

Matched MeSH terms: Heart Rate/drug effects
Fulltext Dose requirement and effect of nicardipine on lipid profile in mild to moderate essential hypertensives

Tariq AR, Maheendran K, Kamsiah J, Christina P

Med J Malaysia, 1992 Sep;47(3):182-9.
PMID: 1491643

Twenty eight patients who satisfied the entry criteria and had completed an initial 2 weeks treatment with placebo were titrated fortnightly with doses of Nicardipine ranging from 30 mg to 90 mg daily in two or three divided doses. Nicardipine treatment significantly reduced blood pressures both in the supine and standing positions (p < 0.0004) when compared with placebo treatment. Heart rates however did not change significantly. Forty six percent (13/28) of patients on 20 mg twice daily, 25% (7/28) on 10 mg three times daily, 18% (5/28) of patients on 20 mg three times daily and 11% (3/28) on 30 mg three times daily achieved supine diastolic blood pressures < 90 mm Hg. Nicardipine treatment at 16 weeks and at 24 weeks did not significantly alter the lipid profile when compared to the end of placebo treatment period. No other biochemical abnormalities were reported during the study period. Except for 2 cases of mild pedal oedema and 2 cases of transient headaches, no serious side-effects were encountered.

Matched MeSH terms: Heart Rate/drug effects
Fulltext Once daily felodipine monotherapy in mild to moderate hypertension

Kon SP, Tan HW, Chua CT, Ong ML, Kamsiah J, Maheendran KK, et al.

Med J Malaysia, 1992 Dec;47(4):290-6.
PMID: 1303482

In a single-blind study conducted at our centres, 78 hypertensive patients were enrolled with 58 completing the study according to the protocol. Mean supine and standing blood pressures were significantly reduced after treatment with felodipine, reductions being 27/21 mmHg (p < 0.0001) and 25/19 mmHg (p < 0.0001) respectively. Of 46 patients given felodipine 5 mg, 44 (95.7%) achieved target blood pressure defined as a diastolic blood pressure of < 90 mmHg, while all 12 patients on felodipine 10 mg did so. The 2 patients who did not achieve target pressure at the final visit did so on previous visits. There were no differences in pre and post-treatment laboratory variables. Treatment was discontinued in 6 patients because of headaches. No adverse events of clinical significance were reported in the 58 patients who completed the study. In conclusion, we found felodipine given once daily to be effective in the treatment of mild to moderate hypertension.

Study site: Multicentre

Matched MeSH terms: Heart Rate/drug effects
Cardiovascular responses in the normotensive rat produced by intravenous injection of gambirine isolated from Uncaria callophylla B1. ex Korth

Mok JS, Chang P, Lee KH, Kam TS, Goh SH

J Ethnopharmacol, 1992 Jun;36(3):219-23.
PMID: 1434680

Among several alkaloids, including dimeric indoles, isolated from Uncaria callophylla, gambirine which is an alkaloid unique to this plant, has been found to be another hypotensive principle from the plant. Intravenous injections of gambirine in the dose range of 0.2 to 10.0 mg/kg caused a dose-related fall in both systolic and diastolic blood pressures as well as heart rate. At all doses gambirine showed a prompt onset of action and at the higher doses (5.0-10 mg/kg), marked persistence of hypotension accompanied by severe bradycardia were observed. In addition, higher doses of gambirine produced a more marked decrease in diastolic than systolic pressure while at lower doses both decreased equally. It is suggested that the hypotensive effect of gambirine may be peripheral in origin and is associated, at least in part, with a cardiac action.

Matched MeSH terms: Heart Rate/drug effects*
Angiotensin-I Converting Enzyme (ACE) Inhibitory and Anti-Hypertensive Effect of Protein Hydrolysate from Actinopyga lecanora (Sea Cucumber) in Rats

Sadegh Vishkaei M, Ebrahimpour A, Abdul-Hamid A, Ismail A, Saari N

Mar Drugs, 2016 Sep 30;14(10).
PMID: 27706040

Food protein hydrolysates are known to exhibit angiotensin converting enzyme (ACE) inhibitory properties and can be used as a novel functional food for prevention of hypertension. This study evaluated the ACE inhibitory potentials of Actinopyga lecanora proteolysate (ALP) in vivo. The pre-fed rats with ALP at various doses (200, 400, 800 mg/kg body weight) exhibited a significant (p ≤ 0.05) suppression effect after inducing hypertension. To determine the optimum effective dose that will produce maximal reduction in blood pressure, ALP at three doses was fed to the rats after inducing hypertension. The results showed that the 800 mg/kg body weight dose significantly reduced blood pressure without noticeable negative physiological effect. In addition, there were no observable changes in the rats' heart rate after oral administration of the ALP. It was concluded that Actinopyga lecanora proteolysate could potentially be used for the development of functional foods and nutraceuticals for prevention and treatment of hypertension.

Matched MeSH terms: Heart Rate/drug effects
Hemodynamic effects of HPMA copolymer based doxorubicin conjugate: A randomized controlled and comparative spectral study in conscious rats

Cheah HY, Šarenac O, Arroyo JJ, Vasić M, Lozić M, Glumac S, et al.

Nanotoxicology, 2017 03;11(2):210-222.
PMID: 28098511 DOI: 10.1080/17435390.2017.1285071

Conjugation of Doxorubicin (DOX) to N-(2-hydroxypropyl) methylacrylamide copolymer (HPMA) has significantly reduced the DOX-associated cardiotoxicity. However, the reports on the impact of HPMA-DOX conjugates on the cardiovascular system such as blood pressure (BP) and heart rate (HR) were in restrained animals using tail cuff and/or other methods that lacked the resolution and sensitivity. Herein, we employed radiotelemetric-spectral-echocardiography approach to further understand the in vivo cardiovascular hemodynamics and variability post administration of free DOX and HPMA-DOX. Rats implanted with radio-telemetry device were administered intravenously with DOX (5 mg/kg), HPMA-DOX (5 mg DOX equivalent/kg) and HPMA copolymer and subjected to continuous cardiovascular monitoring and echocardiography for 140 days. We found that DOX-treated rats had ruffled fur, reduced body weight (BW) and a low survival rate. Although BP and HR were normal, spectral analysis indicated that their BP and HR variabilities were reduced. All rats exhibited typical signs of cardiotoxicity at histopathology. In contrast, HPMA-DOX rats gained weight over time and survived. Although BP, HR and related variabilities were unaffected, the left ventricular end diastolic volume (EDV) of these rats, as well as of the HPMA copolymer-treated rats, was found increased at the end of observation period. Additionally, HPMA copolymer caused microscopic injury of the heart tissue. All of these suggest the necessity of caution when employing HPMA as carrier for prolonged drug delivery. The current study also indicates the potential of radiotelemetric-spectral-echocardiography approach for improved preclinical cardiovascular risk assessment of polymer-drug conjugate and other nano-sized-drug constructs.

Matched MeSH terms: Heart Rate/drug effects*
Effect of bradykinin and its antagonist on survival time after coronary artery occlusion in rats

Atif Abbas S, Sharma JN, Pauzi A, Yusof M

Gen. Pharmacol., 1999 Sep;33(3):243-7.
PMID: 10480657

The present study was conducted to examine the effect of bradykinin and bradykinin 2 receptor antagonist on survival time in rats with coronary artery ligation for 15 min and continuously. We also evaluated the heart rate and blood pressure responses in the presence and absence of bradykinin and its antagonist. Bradykinin treatment (4 microg and 8 microg/kg IV) significantly (p < 0.05) increased the survival time of rats compared with saline-treated rats with coronary artery ligation for 15 min and continuously. The heart rate and blood pressure responses were significantly (p < 0.001) altered in the presence of coronary artery ligation. Bradykinin antagonist treatment (4 microg/kg IV) abolished the effect of bradykinin and thus reduced the survival time of rats with coronary artery ligation. The mean value of survival time between saline-treated and bradykinin antagonist- plus bradykinin-treated rats did not differ significantly (p > 0.05).

Matched MeSH terms: Heart Rate/drug effects

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