Biomedical subjects
Randy M Stevens
Publications and source records attributed to Randy M Stevens.
Adenosine A1/A2a receptor agonist AMP-579 induces acute and delayed preconditioning against in vivo myocardial stunning.
The purpose of this study was to determine whether the adenosine A1/A2a receptor agonist AMP-579 induces acute and delayed preconditioning against in vivo myocardial stunning. Regional stunning was produced by 15 min of coronary artery occlusion and 3 h of reperfusion (RP) in anesthetized open-chest pigs. In acute protection studies, animals were pretreated with saline, low-dose AMP-579 (15 microg/kg iv bolus 10 min before ischemia), or high-dose AMP-579 (50 microg/kg iv at 14 microg/kg bolus + 1.2 microg.kg(-1).min(-1) for 30 min before coronary occlusion). The delayed preconditioning effects of AMP-579 were evaluated 24 h after administration of saline vehicle or high-dose AMP-579 (50 microg/kg iv). Load-insensitive contractility was assessed by measuring regional preload recruitable stroke work (PRSW) and PRSW area. Acute preconditioning with AMP-579 dose dependently improved regional PRSW: 129 +/- 5 and 100 +/- 2% in high- and low-dose AMP-579 groups, respectively, and 78 +/- 5% in the control group at 3 h of RP. Administration of the adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (0.7 mg/kg) blocked the acute protective effect of high-dose AMP-579, indicating that these effects are mediated through A1 receptor activation. Delayed preconditioning with AMP-579 significantly increased recovery of PRSW area: 64 +/- 5 vs. 33 +/- 5% in control at 3 h of RP. In isolated perfused rat heart studies, kinetics of the onset and washout of AMP-579 A1 and A2a receptor-mediated effects were distinct compared with those of other adenosine receptor agonists. The unique nature of the adenosine agonist AMP-579 may play a role in its ability to induce delayed preconditioning against in vivo myocardial stunning.
Sodium-hydrogen exchange inhibition attenuates in vivo porcine myocardial stunning.
BACKGROUND: Inhibition of the sodium-hydrogen exchanger isoform 1 with HOE-642 (cariporide) has been shown to protect against ischemia-reperfusion injury and to decrease myocardial cell death in numerous animal preparations; however the effects of cariporide in stunned myocardium are not as well understood. We sought to determine whether cariporide attenuated myocardial stunning in vivo. METHODS: Open chest anesthetized pigs (22-33 kg) were subjected to 15 min of left anterior descending coronary artery (LAD) occlusion followed by 3 h of reperfusion. Regional ventricular function was assessed by segment shortening. Contractility was measured by stroke work and by load-insensitive preload recruitable stroke work and preload recruitable stroke work area. Vehicle or HOE-642 (1 mg/kg, IV) was administered 10 min before LAD occlusion. RESULTS: Cariporide treatment significantly improved postischemic segment shortening, stroke work, preload recruitable stroke work, and preload recruitable stroke work area and had no systemic hemodynamic effects. After 3 h of reperfusion, control animals recovered 33% +/- 4% and 33% +/- 3% of preischemic LAD segment shortening and preload recruitable stroke work area values, respectively, whereas animals treated with HOE-642 recovered 59% +/- 6% and 57% +/- 6%, respectively (p < 0.05). Seven (39%) of 17 control animals exhibited ventricular fibrillation during reperfusion; none of the cariporide-treated pigs fibrillated. CONCLUSIONS: Sodium-hydrogen exchange inhibition can attenuate postischemic myocardial stunning in addition to its well-described anti-infarct properties. Inhibition of the sodium-hydrogen exchanger may be beneficial in patients susceptible to postischemic myocardial dysfunction associated with cardiac surgery.
Effects of in vivo myocardial ischemia and reperfusion on interstitial nitric oxide metabolites.
BACKGROUND: There have been numerous studies examining the role of nitric oxide (NO) in myocardial ischemia-reperfusion injury; however, few studies have included measurements of NO or related reactive nitrogen species. The purpose of this study was to determine the effects of in vivo regional myocardial ischemia on interstitial fluid (ISF) reactive nitrogen species. METHODS: Open chest pigs were submitted to one of three protocols: (1) 15 minutes coronary occlusion and 2 hours reperfusion, (2) 60 minutes coronary occlusion and 2 hours reperfusion, or (3) two-cycle ischemic preconditioning (IPC) followed by prolonged ischemia and 2 hours reperfusion. The stable NO metabolites, nitrite plus nitrate (NOx), in cardiac microdialysis samples were measured by ozone chemiluminescence. RESULTS: NOx concentration decreased 40% +/- 6% (p < 0.05) during brief ischemia but returned to baseline during reperfusion. Dialysate NOx levels decreased further after 60 minutes ischemia (60% +/- 3% of baseline, p < 0.01) but reperfusion dialysate NOx concentration increased 34% +/- 9% above baseline (p < 0.05). Preconditioning did not increase dialysate NOx but did accelerate the ischemia-induced decrease in NOx levels (p < 0.05). Reperfusion NOx levels in preconditioned pigs were significantly lower than in nonpreconditioned pigs (p < 0.05). CONCLUSIONS: These results suggest that ischemia is associated with decreased ISF NOx concentration. Reperfusion NOx levels are increased after prolonged ischemia, an effect that is significantly blunted by ischemic preconditioning.
Surgical resident education of medical students in the 80-hour workweek.
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Paraesophageal hernia: current diagnosis and treatment.
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