Nicotine does not influence arterial lipid deposits in rabbits exposed to second-hand smoke.

BACKGROUND: Second-hand smoke (SHS) accelerates atherogenesis and impairs vascular function. The role of nicotine in this process has not been defined. METHODS AND RESULTS: To examine the potential effects of nicotine on atherogenesis and vascular function, 48 rabbits receiving a 0.5% cholesterol diet were randomized to control (cholesterol diet only), SHS from nicotine-standard research cigarettes (SHS-ST), and SHS from nicotine-free research cigarettes (SHS-NF). The SHS rabbits were exposed to 48 nicotine-standard (12 animals) or nicotine-free (12 animals) cigarettes/d, 5 d/wk for 10 weeks. Air carbon monoxide and particulates and plasma carboxyhemoglobin were significantly higher in the 2 SHS groups than the control group (P<0.001). The SHS-ST group had significant increases in plasma nicotine and cotinine compared with the other groups (P<0.001). There was no difference in serum lipids. Lipid lesions were increased in both SHS groups (54+/-5% [SEM] aorta and 66+/-4% pulmonary artery, 53+/-7% and 69+/-4%, and 39+/-4% and 43+/-3% in the SHS-ST, SHS-NF, and control groups, respectively; P=0.049 aorta and P<0.001 pulmonary artery). CONCLUSIONS: SHS exposure increased arterial lipid lesions, but nicotine did not contribute significantly to this effect. This effect is presumably due to other combustion products in the smoke.

Comparative effects of ACE inhibitors and an angiotensin receptor blocker on atherosclerosis and vascular function.

BACKGROUND: Both angiotensin-converting enzyme inhibitors (ACE-I(s)) and angiotensin receptor blockers (ARB(s)) provide vascular protection. This study was designed to compare ACE-I(s) with widely differing tissue affinity (captopril and quinapril) and an ARB (losartan) on vascular protection against the adverse effects of high cholesterol. METHODS AND RESULTS: Forty-two New Zealand rabbits on a 0.5% cholesterol diet were randomized into control, captopril (10 mg/kg/d), quinapril (0.3 mg/kg/d), and losartan (8 mg/kg/d) groups for 14 weeks. Captopril, quinapril, and losartan significantly attenuated aortic lipid lesions (P=0.001). Captopril and quinapril were more effective than losartan in preserving vascular relaxation. CONCLUSIONS: Captopril, quinapril, and losartan had similar protective effects against atherogenesis. Captopril and quinapril were more effective than losartan in preserving vascular function. Increased bradykinin by ACE inhibition may be responsible for this improved vascular endothelial function.

Effects of different durations of pretreatment with losartan on myocardial infarct size, endothelial function, and vascular endothelial growth factor.

A previous study by our group showed that 10 weeks of pretreatment with losartan reduced myocardial infarct size and arrhythmias in a rat model of ischaemia-reperfusion. However, the effect of a differing time course of pretreatment has not been investigated. 104 Sprague-Dawley rats were randomised to four groups: a control, and three treatment groups in which losartan (40 mg/kg/day) was administered in drinking water for one day, one week, and four weeks respectively. After different durations of pretreatment, the rats were subjected to 17 minutes of left coronary artery occlusion and 120 minutes of reperfusion. Haemodynamic variables were not significantly different between the four groups. Myocardial infarct size was unchanged after one day and one week of pretreatment (52+/-7, 57+/-6% vs.control 55+/-3%), but was significantly reduced by four weeks of pretreatment with losartan (38+/-6, p<0.05). Endothelial-dependent vasorelaxation was significantly increased by four weeks of pretreatment (-81+/-4 vs.-62+7%, p<0.05). As an indicator of ischaemia, vascular endothelial growth factor (VEGF) levels in ischaemic myocardium were decreased after one and four weeks of pretreatment (0.75+/-0.05, 0.58+/-0.10 vs. 1.0, p<0.05,0.01, respectively). In conclusion, losartan has time-dependent cardiovascular protective effects. Four weeks of pretreatment with losartan decreased infarct size and VEGF, and improved endothelial dysfunction.

Intracoronary measurement of pulsus alternans.

Pulsus alternans is typically found in patients with left ventricular systolic dysfunction. We describe a woman with biventricular systolic dysfunction and pulsus alternans in the right ventricle, pulmonary artery, and aorta. Coronary angiography revealed an intermediate stenosis in the proximal left anterior descending (LAD) coronary artery. Pulsus alternans was demonstrated in the mid LAD using a 0.014" guidewire-mounted pressure sensor. An abnormal fractional flow reserve was measured in the LAD. Cathet. Cardiovasc. Intervent. 51:335-338, 2000.

Comparative effects of pretreatment with captopril and losartan on cardiovascular protection in a rat model of ischemia-reperfusion.

OBJECTIVES: We sought to assess the comparative effects of pretreatment with captopril and losartan on myocardial infarct size and arrhythmias in a rat model of ischemia-reperfusion. BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) inhibit the renin-angiotensin system in different ways. However, the comparative effects of pretreatment with ACE inhibitors or ARBs on acute myocardial infarct size and arrhythmias are unknown. METHODS: We randomly assigned 117 female Sprague-Dawley rats into three groups: group N was the normal control; group C was given 40 mg/kg body weight per day of captopril in drinking water; and group L was given 40 mg/kg per day of losartan in drinking water. After 10 weeks of pretreatment, 25 rats in each group were subjected to 17 min of left anterior descending coronary artery occlusion and 2 h of reperfusion with hemodynamic and electrocardiographic monitoring. Fourteen rats in each group had blood samples drawn and aortic rings removed to study vascular reactivity. RESULTS: Mortality during ischemia and reperfusion was lower in combined groups L and C than in group N (4.2% vs. 19.2%, p = 0.042). Rats treated with losartan had significantly higher levels of angiotensin II in their plasma. Hemodynamic variables were not significantly different among the three groups. The thresholds of ventricular fibrillation (VF) before occlusion and after reperfusion were significantly higher in groups L and C than in group N (1.99 +/- 0.24 and 1.93 +/- 0.27 vs. 1.23 + 0.17 mA, p = 0.04; 2.13 +/- 0.25 and 1.78 +/- 0.22 vs. 0.95 +/- 0.11 mA, p = 0.001). The average episodes of ventricular tachycardia (VT) and VF per rat were significantly less in groups L and C than in group N (0.96 +/- 0.2 and 1.2 +/- 0.3 vs. 2.8 + 0.4 mA, p < 0.001). Myocardial infarct size was significantly smaller in groups L and C than in group N (34 +/- 3% and 35 +/- 3% vs. 44 +/- 3%, p = 0.031, 0.043). Endothelium-dependent vasorelaxation induced by a calcium ionophore (A23187) was increased in both groups but was only statistically significant in group C (p = 0.020). CONCLUSIONS: Losartan and captopril have similar cardiovascular protective effects in a rat model of ischemia-reperfusion. They increased the threshold of VF, decreased mortality and decreased episodes of VT and VF, as well as decreased myocardial infarct size.

Effects of second-hand smoke and gender on infarct size of young rats exposed in utero and in the neonatal to adolescent period.

OBJECTIVES: We sought to assess the effects of second-hand smoke (SHS) and gender on infarct size in young rats exposed in utero or in the neonatal to adolescent period, or both. BACKGROUND: We previously demonstrated that exposure to SHS increases infarct size in a rat model of ischemia and reperfusion, with a dose-response relation. These results are consistent with epidemiologic studies demonstrating that SHS increases risk of death from heart disease. METHODS: Thirty-one pregnant female rats were randomly divided into two groups: those exposed to SHS and a control group (non-SHS). After 3 weeks, each rat had given birth to 10 to 12 rats. One hundred one neonatal rats were divided into four groups according to exposure to SHS in utero (SHSu) and randomized to SHS exposure in the neonatal to adolescent period (SHSna). After 12 weeks, all rats were subjected to 17 min of left coronary artery occlusion and 2 h of reperfusion. RESULTS: Birth mortality was higher in the SHSu group than in the non-SHSu group (11.9% vs. 2.8%, p < 0.001). Body weight of neonatal rats at 3 and 4 weeks in the two SHSu groups was lower than that of rats in the two non-SHSu groups (p < 0.001). Exposure to SHSna increased endothelin-1 levels in plasma (p = 0.001). In all 70 young rats who survived the neonatal period, infarct size (Infarct mass/Risk area x 100%) was greater in the SHSna groups than in the non-SHSna groups (p = 0.005) and in the male groups than in the female groups (p < 0.001). CONCLUSIONS: Exposure to SHS in the neonatal to adolescent period and male gender increased myocardial infarct size in a young rat model of ischemia and reperfusion. These results are consistent with epidemiologic studies demonstrating that SHS increases the health risk to neonates and adolescents.