METHODS: An initial study showed that PMX53, an antagonist of C5aR1 in normal C57BL6/J (wild type, WT) mice reduced heart rate (HR) and appeared to have a protective effect on the heart following induced sepsis. C5aR1 knockout (CD88-/-) mice had a lower HR than wild type mice, even during sham surgery. A model to assess heart rate variability (HRV) in anesthetized mice was developed to assess the effects of inhibiting the β1-adrenoreceptor (β1-AR) in a randomized crossover study design.
RESULTS: HR and LF Norm were constitutively lower and SDNN and HF Norm constitutively higher in the CD88-/- compared with WT mice (P< 0.001 for all outcomes). Administration of atenolol (2.5 mg/kg) reduced the HR and increased HRV (P< 0.05, respectively) in the wild type but not in the CD88-/- mice. There was no shift of the sympathovagal balance post-atenolol in either strains of mice (P> 0.05), except for the reduced LF/HF (Lower frequency/High frequency) ratio (P< 0.05) at 60 min post-atenolol, suggesting increased parasympathetic tone of the heart due to the effect of atenolol administration. The HR of the WT mice were lower post atenolol compared to the CD88-/- mice (P = 0.001) but the HRV of CD88-/- mice were significantly increased (P< 0.05), compared with WT mice.
CONCLUSION: Knockout of the C5aR1 attenuated the effect of β1-AR in the heart, suggesting an association between the β1-AR and C5aR1, although further investigation is required to determine if this is a direct or causal association.
METHODS: Revascularised acute myocardial infarction patients with normal left ventricular (LV) systolic function on TTE were assessed by 1.5T CMR. Acute regional diastolic wall motion abnormalities, global diastolic function measurements, acute segmental damage fraction with LGE and mean segmental pre-contrast T1 values were assessed on matching short axis slices.
RESULTS: Forty-four patients were analysed. Mean LVEF was 62.1±9.4%. No difference between NSTEMI (22/44) and STEMI in mean pre-contrast T1 values of infarcted (1025.0±109.2 vs 1011.0±81.6ms, p=0.70), adjacent (948.3±45.3 vs 941.1±46.6ms, p=0.70) and remote (888.8±52.8 vs 881.2±54.5ms, p=0.66) segments was detected. There was no correlation between pre-contrast T1 of infarcted segments with global diastolic dysfunction (E/A, r(2)=0.216, p=0.06; S/D, r(2)=0.243, p=0.053; E/E', r(2)=0.240, p=0.072), but there was significantly positive, moderate correlation with circumferential diastolic strain rate, (r(2)=0.579, p<0.01) with excellent agreement and reproducibility.
CONCLUSION: Cardiac magnetic resonance evaluation of pre-contrast T1 values revealed no difference between NSTEMI and STEMI patients in terms of tissue characterisation post-myocardial infarction. However, pre-contrast T1 of infarcted tissue is significantly correlated with regional diastolic circumferential strain rate.