Moderate systemic hypotension during reperfusion reduces the coronary blood flow and increases the size of myocardial infarction in pigs

Study objectives: To examine the effects of low arterial BP (ABP) during reperfusion on the extent of myocardial infarction and on coronary blood flow (CBF) in an occlusion/reperfusion experimental model. Design: Prospective, randomized animal study. Setting: University hospital. Participants: Normal pigs that were anesthetized, intubated, and mechanically ventilated. Interventions: Twenty-seven open-chest pigs underwent occlusion of the mid left anterior descending (LAD) coronary artery for I h followed by reperfusion for 2 h. During reperfusion, the animals were randomly assigned to either continuous infusion of nitroglycerin in therapeutic doses and fluid infusion at rates to maintain a mean ABP greater than or equal to 80 mm Hg (group 1, n = 13), or continuous nitroglycerin infusion at rates to maintain a mean ABP between 60 mm Hg and 75 mm Hg (group 2, n = 14). Measurements and results: The hemodynamics and the coronary ABP distal to the occlusion were recorded throughout the experiment. In addition, the LAD CBF and peak hyperemia CBF before occlusion and during reperfusion periods were measured by transit-time flowmetry. At the end of the experiment, the infareted left ventricular myocardial size was measured. There were no significant hemodynamic differences, including the distal coronary arterial pressure, between the two groups before or during the LAD artery occlusion period. During reperfusion, mean ABP was 90 +/- 3 min Hg in group 1 vs 69 +/- 3 mm Hg in group 2 (p < 0.001). In group 1, the infarcted myocardium represented 50.3 +/- 4.3% of the myocardium at risk, vs 69.4 +/- 7.2% in group 2 (p < 0.001). During reperfusion, CBF and peak hyperemia CBF were significantly higher in group 1 than in group 2. Conclusions: Low ABP during reperfusion increases the size of myocardial infarction and decreases CBF

Insights Into Myocardial Oxygen Consumption, Energetics, and Efficiency Under Left Ventricular Assist Device Support Using Noninvasive Pressure-Volume Loops.

BACKGROUND: Assessment of left ventricular (LV) recovery under continuous-flow LV assist device therapy is hampered by concomitant pump support. We describe derivation of noninvasive pressure-volume loops in continuous-flow LV assist device patients and demonstrate an application in the assessment of recovery. METHODS AND RESULTS: Using pump controller parameters and noninvasive arterial pressure waveforms, central aortic pressure, outflow conduit pressure gradient, and instantaneous LV pressure were calculated. Instantaneous LV volumes were calculated from echocardiographic LV end-diastolic volume accounting for the integral of pump flow with respect to time and aortic ejection volume derived from the pump speed waveform. Pressure-volume loops were derived during pump speed adjustment and following bolus intravenous milrinone to assess changes in loading conditions and contractility, respectively. Fourteen patients were studied. Baseline noninvasive LV end-diastolic pressure correlated with invasive pulmonary arterial wedge pressure (r2=0.57, root mean square error 5.0 mm Hg, P=0.003). Measured noninvasively, milrinone significantly increased LV ejection fraction (40.3±13.6% versus 36.8±14.2%, P<0.0001), maximum dP/dt (623±126 versus 555±122 mm Hg/s, P=0.006), and end-systolic elastance (1.03±0.57 versus 0.89±0.38 mm Hg/mL, P=0.008), consistent with its expected inotropic effect. Milrinone reduced myocardial oxygen consumption (0.15±0.06 versus 0.16±0.07 mL/beat, P=0.003) and improved myocardial efficiency (43.7±14.0% versus 41.2±15.5%, P=0.001). Reduced pump speed caused increased LV end-diastolic volume (190±80 versus 165±71 mL, P<0.0001) and LV end-diastolic pressure (14.3±10.2 versus 9.9±9.3 mm Hg, P=0.024), consistent with a predictable increase in preload. There was increased myocardial oxygen consumption (0.16±0.07 versus 0.14±0.06 mL O2/beat, P<0.0001) despite unchanged stroke work (P=0.24), reflecting decreased myocardial efficiency (39.2±12.7% versus 45.2±17.0%, P=0.003). CONCLUSIONS: Pressure-volume loops are able to be derived noninvasively in patients with the HeartWare HVAD and can detect induced changes in load and contractility

Comparison of pulsatile with nonpulsatile mechanical support in a porcine model of profound cardiogenic shock

The aim of this study was to examine whether pulsatility by intraaortic balloon counterpulsation (IABP) is an important adjunct to the treatment of profound cardiogenic shock (CS) with a widely used, nonpulsatile centrifugal pump (CP). In each of 18 anesthetized, open chest pigs, the outflow cannula of the CP was inserted in the aortic arch through the right external carotid artery, and the inflow cannula of the CP was placed in the left atrium. A 40 cc IABP was subsequently placed in the descending aorta through the left external carotid artery. CS was induced by occlusion of coronary arteries and the infusion of propranolol and crystalloid fluid. Mean aortic pressure, pulse pressure, aortic end diastolic pressure, left ventricular end diastolic pressure, right atrial pressure, and heart rate were monitored. Cardiac output and left anterior descending artery flow were measured with a transit time ultrasound flowmeter. During profound CS, life sustaining hemodynamics were maintained only with the support of the assist devices. Hemodynamic support with the CP was associated with a nearly nonpulsatile flow and a pulse pressure of 7 +/- 4 mm Hg, which increased to 33 +/- 10 mm Hg (p = 0.000) after combining the CP with the IABP. Compared with the hemodynamic support offered by the CP alone, addition of the IABP increased mean aortic pressure from 40 +/- 15 to 50 +/- 16 mm Hg (p = 0.000), cardiac output from 810 +/- 194 to 1,200 +/- 234 ml/min (p = 0.003), and left anterior descending artery flow from 26 10 to 39 14 ml/min (p = 0.001). In profound CS, mechanical support provided by a continuous flow CP is enhanced by the added pulsatility of the IABP

Prevalence and prognostic significance of anemia in patients with congestive heart failure treated with standard vs high doses of enalapril

Background: Anemia is common in patients with congestive heart failure (CHF), although its etiology and pathophysiology remain largely unexplained. The purpose of this study was to examine the prognostic significance of a low hematocrit (Hct) in patients with CHF and the possible role of angiotensin-converting enzyme inhibition in anemia development. Methods: Hct was measured at the time of enrollment of 160 patients with CHF, mean age 56 12 years, in New York Heart Association (NYHA) functional class 2.6 +/- 0.7 and with left ventricular ejection fraction of 20 +/- 9%. They were randomized to standard (mean: 17.9 +/- 4.3 mg/day) or high (mean: 42 +/- 19.3 mg/day) doses of enalapril. The follow-up duration was 2 years. Cox regression models were used to identify prognostic factors, and correlations among individual variables were tested. Results: Mean baseline Hct was 42.7 +/- 5%. In multivariate analyses, low Hct (p = 0.036), older age (p = 0.022) and low systolic blood pressure (p = 0.032) were independent predictors of death within 2 years. A correlation was found between baseline Hct and NYHA class (Spearman’s correlation coefficient: -0.183, p = 0.008). A significant decrease in Hct from 43.2 +/- 4.9% at baseline to 40.7 +/- 4.4% at 2 years was observed in the group treated with high doses of enalapril (p &lt; 0.001). Conclusions: Low baseline Hct predicted poor 2-year prognosis in patients with CHF. Enalapril administered in high doses increased the incidence of anemia in this population. The underlying pathophysiologic mechanism and effects of maintaining a normal Hct on clinical outcomes remain to be determined

Myocardial ischaemic preconditioning in the pig has no effect on the ventricular fibrillation and defibrillation thresholds

Introduction: The effects of myocardial ischaemia preconditioning in pigs on the vulnerability to ventricular fibrillation during subsequent ischaemic events are controversial. This study examined the time course of changes in ventricular fibrillation (VFT) and defibrillation (DFT) thresholds during transient myocardial ischaemia after a 45 min preconditioning period. Methods and results: In five open-chest pigs, VFT was measured after 3 min of regional myocardial ischaemia, at time 0, 2, 15, 30, 60 and 90 min (Control group). In seven other pigs (Test group), VFT was measured before (time 0) and 2, 15, 30, 60 and 90 min after ischaemic preconditioning by three consecutive 5 min periods of regional coronary occlusion, followed by 10 min of reperfusion. DFT was measured by increasing the stored energy systematically until successful defibrillation. Ischaemic preconditioning caused no significant change in the effective refractory period (ERP), VFT or DFT over the 90 min of the experiments. In the Control group, ERP remained stable for 30 min, though was significantly lower at 90 min (178 +/- 28 ms) than at baseline (204 +/- 32 ms, P = 0.007). VFT and DFF remained unchanged throughout the experiments, and no difference was observed in ERP, VFT and DFT between the two groups at any time during the experiment. Conclusion: No changes were observed in the refractory duration, ventricular vulnerability or defibrillation energy requirements up to 90 min after ventricular ischaemic preconditioning in the pig. (c) 2004 Elsevier Ireland Ltd. All rights reserved