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.

Hemodynamic effects of levosimendan in acute myocardial infarction complicated by cardiogenic shock and high systemic vascular resistance.

BACKGROUND: Levosimendan (LEVO), a new inodilator, improves hemodynamic function in patients with decompensated heart failure and preserved arterial blood pressure. Data on its use in patients with cardiogenic shock (CS) are scarce. The present study was undertaken to evaluate the hemodynamic effects of supplemental therapy with levosimendan (LEVO) in acute myocardial infarction (MI) and refractory cardiogenic shock (CS). METHODS: In 25 patients presenting in CS after acute MI, LEVO was administered for 24 h in doses ranging between 0.05 and 0.20 microg/kg/min, as tolerated, preceded by 6-microg/kg over 10 min, in addition to catecholamines. Hemodynamic measurements were made before and 24 h after initiation of the LEVO infusion. RESULTS: Hemodynamic improvement was limited to 13 patients with systemic vascular resistances (SVR) > or =18 W. LEVO increased the cardiac index from 1.5+/-0.3 l/min/m2 to 2.1+/-0.4 l/min/m2 (P = 0.002) and cardiac power from 0.462+/-0.164 W to 0.645+/-0.179 W (P = 0.022), and decreased SVR from 23+/-5 to 21+/-6.7 Wood units (P = 0.001) and pulmonary capillary wedge pressure from 24+/-9 mmHg to 16+/-11 mmHg (P = 0.059). No hemodynamic improvement was observed during LEVO administration in 12 patients with SVR < 18 W. CONCLUSION: The hemodynamic benefit conferred by LEVO added to catecholamines in patients with CS after acute MI was limited to patients with high SVR.

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.

Immune status evaluation of patients with chronic heart failure.

Chronic heart failure (CHF) may be considered a state of immune activation and persistent inflammation expressed by increased circulating levels of pro- and anti-inflammatory cytokines. The purpose of the study was to investigate the immune status in patients with CHF compared to normal individuals. We measured serum cytokine levels as well as cytokine production after ex vivo LPS stimulation of whole blood taken from 14 patients with CHF and 14 healthy volunteers. We used 500 pg/ml of LPS for an incubation period of 4h to stimulate 100 microL of whole blood. Patients with CHF had significantly higher levels of TNF-RI, and TNF-RII in serum compared to normal individuals. TNF-alpha, IL-6, and IL-10 did not differ significantly. After LPS stimulation, patients with CHF had significantly higher levels of TNF-alpha and IL-10, and significantly lower IL-6 levels compared to normal individuals. TNF-alpha receptors did not differ significantly. Patients with CHF may be found in a pro- as well as an anti-inflammatory state. They also do not develop endotoxin tolerance in an ex vivo laboratory model using whole blood stimulated with LPS. They may have increased TNF-alpha and IL-10 production after LPS stimulation of whole blood, which may contribute to a worsening of heart function, more severe disease presentation and a worse outcome during infections.

Circulating adiponectin levels and expression of adiponectin receptors in relation to lung cancer: two case-control studies.

BACKGROUND: Decreased circulating levels of adiponectin, an adipocyte-secreted hormone and endogenous insulin sensitizer, have been associated with several obesity-related malignancies. Thiazolidinedione administration, which increases adiponectin levels, decreases risk for lung cancer. Whether circulating adiponectin levels are associated with lung cancer and/or whether adiponectin receptors are expressed in lung cancer remains unknown. METHODS: We conducted a case-control study of 85 patients with incidental, histologically confirmed lung cancer and 170 healthy controls matched by gender and age. In a separate study, archival lung specimens from 134 cancerous and 8 noncancerous tissues were examined for relative expression of adiponectin receptors AdipoR1 and AdipoR2 using immunohistochemistry. RESULTS: Tobacco smoking, heavy alcohol intake and education were all associated with lung cancer risk, whereas serum adiponectin levels were not significantly different between cases and controls (multiple logistic regression, odds ratio per SD of adiponectin among controls: 1.13, 95% confidence interval: 0.64-2.02). Adiponectin levels were significantly lower (odds ratio: 0.25, 95% confidence interval: 0.10-0.78) among patients with advanced compared to those with limited disease stage. Expression of adiponectin receptors was apparent only in the cancerous lung tissue (64.2% AdipoR1 and 61.9% AdipoR2 in cancerous vs. 0% among noncancerous tissue). Specifically, AdipoR1 was expressed in all disease types, but no difference was noted with disease stage, whereas AdipoR2 was mainly expressed in the non-small cell carcinomas and more prominently in the advanced disease stage (80%). CONCLUSIONS: Circulating adiponectin levels are not different in cases of this malignancy - which seems to be unrelated to obesity and insulin resistance - compared to their healthy controls, though hormonal levels were significantly lower in advanced versus limited lung cancer. Both adiponectin receptors were expressed in cancerous lung tissue, but not in normal control tissue and there was a differential expression by disease stage. These findings should be further explored, especially in the context of the recently reported protective effect of thiazolidinediones in diabetic patients with lung cancer.