The renin-angiotensin system does not contribute to the endothelial dysfunction and increased infarct size in rats exposed to second hand smoke.

INTRODUCTION: Both second hand smoke (SHS) and the renin-angiotensin system (RAS) contribute to endothelial dysfunction and increased infarct size in a rat ischaemia-reperfusion model. However, the potential interaction between SHS and the RAS is unknown. METHODS: Eighty-four rats were randomised into four groups: group C was a normal control; L was given 40 mg/kg/day of losartan in drinking water; SC and SL were exposed to SHS (smoking chamber) and given regular water or 40 mg/kg/day of losartan in drinking water, respectively. After six weeks of pre-treatment, rats were subjected to 17 minutes of left coronary artery occlusion and 2 hours of reperfusion with haemodynamic and ECG monitoring. RESULTS: Haemodynamics were not significantly different among the four groups. Losartan increased the threshold for ventricular fibrillation (p=0.0001) and reduced spontaneous ventricular arrhythmias (p=0.002) during ischaemia-reperfusion, while SHS did not (p=0.713, 0.110), and there was no interaction between losartan and SHS. The maximal endothelium-dependent vasorelaxation induced by a calcium ionophore (A23187) was increased by losartan (p=0.007). Myocardial infarct size was smaller in the losartan groups (p=0.032), larger in the SHS groups (p=0.0001), and there was no significant interaction. CONCLUSION: In conclusion, losartan decreased infarct size and increased endothelium-dependent vasorelaxation. SHS exposure impaired endothelial function and increased infarct size. The effects of losartan and SHS were consistently independent of each other. These results suggest that the RAS does not contribute to the adverse effects of SHS.

Effect of endovascular cooling on myocardial temperature, infarct size, and cardiac output in human-sized pigs.

Mild hypothermia reduces myocardial infarct size in small animals; however, the extent of myocardial protection in large animals with greater thermal mass remains unknown. We evaluated the effects of mild endovascular cooling on myocardial temperature, infarct size, and cardiac output in 60- to 80-kg isoflurane-anesthetized pigs. We occluded the left anterior descending coronary artery for 60 min, followed by reperfusion for 3 h. An endovascular heat-exchange catheter was used to either lower core body temperature to 34 degrees C (n = 11) or maintain temperature at 38 degrees C (n = 11). Additional studies assessed myocardial viability and microvascular perfusion with (99m)Tc-sestamibi autoradiography. Endovascular cooling reduced infarct size compared with normothermia (9 +/- 6% vs. 45 +/- 8% of the area at risk; P < 0.001), whereas the area at risk was comparable (19 +/- 3% vs. 20 +/- 7%; P = 0.65). Salvaged myocardium showed normal sestamibi uptake, confirming intact microvascular flow and myocyte viability. Cardiac output was maintained in hypothermic hearts because of an increase in stroke volume, despite a decrease in heart rate. Mild endovascular cooling to 34 degrees C lowers myocardial temperature sufficiently in human-sized hearts to cause a substantial cardioprotective effect, preserve microvascular flow, and maintain cardiac output.