Effects of L-NAME on coronary blood flow, infarct size and the extent of the no-reflow phenomenon.

BACKGROUND: NOS inhibitors are a potential treatment for patients with cardiogenic shock during acute myocardial infarction. Despite hemodynamic efficacy, their effects on the extent of myocardial infarction (MI) and the no-reflow phenomenon (NRP) have not been clarified. METHODS: Sixteen pigs underwent occlusion of the mid left anterior descending coronary artery for 1h followed by reperfusion for 2h. Coronary blood flow (CBF), distal to the occlusion site, was measured. In eight experiments, L-NAME (non selective NO synthetase inhibitor) administration began 10 min before the onset of reperfusion and continued for 2h (loading dose 1mg/kg, perfusion rate: 1mg/kg/h) (L-NAME group). Eight pigs received similarly normal saline (controls). At the end of each experiment, the myocardial area at risk (MAR) and extent of MI and NRP were measured. RESULTS: Hemodynamics at baseline and during ischemia were similar in both groups. During reperfusion, the mean aortic blood pressure was significantly higher in the l-NAME group. In both groups, CBF reached a peak at 5 min of reperfusion, (no difference between groups). CBF gradually returned to baseline levels within 60 min of reperfusion in both groups. No statistically significant differences in the extent of the NRP (51.8 ± 19.7 vs 60.9 ± 11.4 p=0.35) and MI (77.9 ± 13.9 vs 77.1 ± 8.8 p=0.92), both expressed as a percentage of MAR, were observed between the L-NAME group and the control group. CONCLUSIONS: L-NAME administration started immediately before and maintained throughout reperfusion has no effect on NRP and MI size. L-NAME might stabilize patients with post-MI cardiogenic shock without adverse effects on infarct size.

Intra-aortic balloon counterpulsation and delayed revascularization for myocardial infarction and shock in the absence of primary angioplasty: a treatment strategy with or without thrombolysis?

OBJECTIVE: When revascularization facilities are not available, thrombolytic therapy (TT) added to intra-aortic balloon counterpulsation (IABC) has been proposed as initial therapy for the management of patients presenting with postmyocardial infarction (MI) cardiogenic shock, followed by prompt transfer to another institution for revascularization. The use of TT in this setting, however, remains controversial. METHODS: We reviewed the records of 81 consecutive patients admitted with cardiogenic shock after acute MI and compared the outcomes of patients initially stabilized, including IABC as an adjunct to TT (IABC+TT group, n=40), with those patients initially stabilized with IABC and no TT (IABC group, n=41). RESULTS: The baseline characteristics of the two study groups were similar. The in-hospital and 6-month survival rates were 47.5 and 33.3% in the IABC+TT group versus 43.9 and 31.6% in the IABC group, respectively (NS). Except for mechanical ventilation more frequently required in the IABC group, other outcome measures were similar in both groups. The in-hospital (76.5 vs. 36.5%, P=0.008) and 6-month (60 vs. 25.4%, P=0.01) survival rates were significantly higher in patients who underwent delayed invasive revascularization, than in patients who underwent no invasive revascularization attempt. CONCLUSION: In patients presenting with acute MI and cardiogenic shock, TT as an adjunct to IABC added no therapeutic benefit when compared with IABC alone. In contrast, the survival of patients was significantly increased by delayed invasive revascularization in both treatment groups. These observations suggest that, when revascularization facilities are not available, stabilization with IABC, followed by prompt transfer for delayed revascularization to a tertiary care hospital, might be the preferred management strategy for patients presenting with post-MI cardiogenic shock.

Inotropic agents improve the peripheral microcirculation of patients with end-stage chronic heart failure.

BACKGROUND: Skeletal muscle microcirculation impairment in patients with chronic heart failure (CHF) seems to correlate with disease severity. We evaluated the microcirculation by near-infrared spectroscopy (NIRS) occlusion technique before and after inotropic infusion. METHODS: We evaluated 25 patients with stable CHF, 30 patients with end-stage CHF (ESCHF) receiving treatment with intermittent infusion of inotropic agents, and 12 healthy subjects. Thenar muscle tissue oxygen saturation (StO(2)%) was measured noninvasively by NIRS before, during, and after 3-minute occlusion of the brachial artery (occlusion technique) in all subjects and in patients with ESCHF before and after 6 hours of inotropic infusion (dobutamine and/or levosimendan) or placebo (N = 5). RESULTS: Patients with ESCHF or CHF presented significantly lower StO(2)% than healthy subjects (74.5% +/- 7%, 78.6% +/- 6%, and 85% +/- 5%, respectively; P = .0001), lower oxygen consumption rate during occlusion (24.6% +/- 8%/min, 28.6% +/- 10%/min, and 38.1% +/- 11.1%/min, respectively; P = .001), and lower reperfusion rate (327% +/- 141%/min, 410% +/- 106%/min, and 480% +/- 133%/min, respectively; P = .002). After 6 hours of inotropic infusion, patients with ESCHF showed significantly increased StO(2)% (74.5% +/- 7% to 82% +/- 9%, P = .001), oxygen consumption rate (24.6% +/- 8%/min to 29.3% +/- 8%/min, P = .009), and reperfusion rate (327% +/- 141%/min to 467% +/- 151%/min, P = .001). No statistical difference was noted in the placebo group. CONCLUSION: Peripheral muscle microcirculation as assessed by NIRS is impaired in patients with CHF. This impairment is partially reversed by infusion of inotropic agents in patients with ESCHF.

The effects of exercise training on the kinetics of oxygen uptake in patients with chronic heart failure.

BACKGROUND: Prolonged oxygen uptake kinetics (O2 kinetics), following the onset of a constant workload of exercise has been associated with a poor prognosis in patients with chronic heart failure. This study aimed to determine both continuous and interval training effects on the different O2-kinetics phases in these patients. DESIGN: Twenty-one patients (60+/-8 years) with stable chronic heart failure participated in a 36-session exercise rehabilitation program (three times weekly). Patients were randomly assigned to interval training (n=11; 100% of peak work rate for 30 s, alternating with 30 s-rest) and to continuous training (n=10; 50% of peak work rate). METHODS: Before and after the completion of the program, all patients performed both incremental symptom-limited and constant workload submaximal cardiopulmonary exercise tests. Phase I O2-kinetics was evaluated by time (t), from the start of exercise until the onset of decreased respiratory exchange ratio and phase II by the time constant (tau) of the response from the end of phase I until steady state. RESULTS: After training, there was a significant increase in peak oxygen uptake and peak work rate in both continuous (15.3+/-4.4 vs. 16.6+/-4.5 ml/kg per min; P=0.03 and 81.8+/-40.1 vs. 94.7+/-46.1 W; P=0.03) and interval training groups (14.2+/-3.1 vs. 15.4+/-4.2 ml/kg per min; P=0.03 and 82.5+/-24.1 vs. 93.7+/-30.1 W; P=0.04). Patients who underwent interval training had a significant decrease in t (39.7+/-3.7 to 36.1+/-6.9 s; P=0.05), but not tau (59.6+/-9.4 to 58.9+/-8.5 s; P=ns), whereas those assigned to continuous training had a significant decrease in both t (40.6+/-6.1 to 36.4+/-5.4 s; P=0.01) and tau (63.3+/-23.6 to 42.5+/-16.7 s; P=0.03). CONCLUSIONS: Exercise training improves O2 kinetics in chronic heart failure patients. Both continuous and interval training improve phase I O2-kinetics, but continuous training results in superior improvement of the phase II O2-kinetics, an indirect index of muscle oxidative capacity.

Pulmonary function at peak exercise in patients with chronic heart failure.

BACKGROUND: Various respiratory abnormalities are associated with chronic heart failure (CHF). However, changes in inspiratory capacity (IC) and breathing pattern from rest to exercise in patients with CHF have not been thoroughly investigated in these patients. MATERIALS AND METHODS: Seventy seven (66 male/11 female) patients with clinical stable CHF (age: 52+/-11 years) were studied. All the patients underwent pulmonary function tests, including measurements of IC and maximal inspiratory pressure (Pimax) at rest and then a maximal cardiopulmonary exercise testing (CPET) on a treadmill. During the CPET, IC was measured every 2 min. Pimax was measured again after the end of CPET. RESULTS: Percent predicted forced expiratory volume in 1 s (FEV1) was 91+/-12, %predicted forced vital capacity (FVC) was 92+/-13, %FEV1/FVC was 81+/-4, and %predicted IC was 85+/-18. Peak exercise IC was lower than resting (2.4+/-0.6 vs. 2.6+/-0.6 l, p<0.001). Analysis of variance between Weber's groups revealed statistically significant differences in peak exercise IC (p<0.001), VE/VCO2slope (p<0.001), resting Pimax (p=0.005) and post-exercise Pimax (p<0.001). At rest, there was a statistically significant difference in end-tidal CO2 (P(ETCO2)) (p=0.002), in breathing frequency (p=0.004), in inspiratory time (Ti) (p=0.04) and in total respiratory time (T(Tot)) (p=0.004) among Weber's groups. At peak exercise there was a statistically significant decrease in minute ventilation (VE) (p<0.001), tidal volume (VT) (p<0.001), respiratory cycle (VT/TI) (p<0.001) and P(ETCO2) (p<0.001). Peak IC was correlated with peak VO2 (r=0.72, p<0.001), anaerobic threshold (r=0.71, p<0.001), VO2/t slope (r=0.54, p<0.0001), and post-exercise Pimax (r=0.62, p<0.001). CONCLUSIONS: In patients with CHF, peak exercise IC is reduced in parallel with disease severity, which is probably due to respiratory muscle dysfunction.