Ischemia In Dogs Research Articles

Monophosphoryl lipid A attenuates myocardial stunning in dogs: role of ATP-sensitive potassium channels.

Results of previous studies indicate that monophosphoryl lipid A (MLA) reduces myocardial infarct size when administered 24 but not 1 h before a prolonged period of regional ischemia in dogs and rabbits. This cardioprotective effect of MLA could be reversed by the administration of the adenosine triphosphate (ATP)-sensitive potassium channel (K(ATP)) blockers, glibenclamide, or 5-hydroxydecanoate. MLA also was shown to attenuate myocardial stunning in dogs; however, its mechanism in this model remains unknown. Therefore the major aim of our study was to determine the dose-related effect of MLA to enhance contractile function in stunned myocardium and to determine the role of the K(ATP) channel in mediating its cardioprotective effect. To produce myocardial stunning, barbital-anesthetized dogs were subjected to five cycles of 5 min of left anterior descending (LAD) coronary artery occlusion interspersed with 10 min of reperfusion and finally followed by 2 h of reperfusion. Regional segment shortening (%SS) was determined by sonomicrometers implanted in the subendocardium of the ischemic region. Single intravenous doses of MLA in the range of 10-35 microg/kg given 24 h before ischemia resulted in an improvement in %SS over a 2-h reperfusion period. Similar to results obtained in the canine and rabbit infarct models, cardioprotection against stunning with MLA appears to require activation of K(ATP) channels during ischemia, because glibenclamide (50 microg/kg, 15 min before ischemia) completely blocked the effect of MLA to improve regional %SS during reperfusion. Cardioprotective doses of MLA were without effect on systemic hemodynamics, blood gases, and pH throughout the experiment. No treatment-related effects on regional myocardial blood flow were observed during ischemia or reperfusion. These results suggest that MLA improves %SS at doses of 10-35 microg/kg by an ATP-sensitive potassium channel-dependent process, and that MLA may mimic the antistunning effects observed during the second window of ischemic preconditioning.

Protein kinase C expression and activity after global incomplete cerebral ischemia in dogs.

Studies suggest that protein kinase C (PKC) activation during ischemia plays an important role in glutamate neurotoxicity and that PKC inhibition may be neuroprotective. We tested the hypothesis that elevations in the biochemical activity and protein expression of Ca2+-dependent PKC isoforms occur in hippocampus and cerebellum during the period of delayed neurodegeneration after mild brain ischemia. We used a dog model of 20 minutes of global incomplete ischemia followed by either 6 hours, 1 day, or 7 days of recovery. Changes in PKC expression (Western blotting and immunocytochemistry) and biochemical activity were compared with neuropathology (percent ischemically damaged neurons) by means of hematoxylin and eosin staining. The percentage of ischemically damaged neurons increased from 13+/-4% to 52+/-10% in CA1 and 24+/-11% to 69+/-6% in cerebellar Purkinje cells from 1 to 7 days, respectively. The occurrence of neuronal injury was accompanied by sustained increases in PKC activity (240% and 211% of control in hippocampus and cerebellum, respectively) and increased protein phosphorylation as detected by proteins containing phosphoserine residues. By Western blotting, the membrane-enriched fraction showed postischemic changes in protein expression with increases of 146+/-64% of control in hippocampal PKCalpha and increases of 138+/-38% of control in cerebellar PKCalpha, but no changes in PKCbeta and PKCgamma were observed. By immunocytochemistry, the neuropil of CA1 and CA4 in hippocampus and the radial glia in the molecular layer of cerebellum showed increased PKCalpha expression after ischemia. This study shows that during the period of progressive ischemic neurodegeneration there are regionally specific increases in PKC activity, isoform-specific increases in membrane-associated PKC, and elevated protein phosphorylation at serine sites.

The effects of FK409, a novel nitric oxide donor, on extended liver resection with ischemia in dogs

The effects of FK409, a novel nitric oxide donor, on extended liver resection with ischemia in dogs

The effect of FR167653 on extended liver resection with ischemia in dogs: Investigation of optimal duration of FR167653 administration and expression of IL-8

The effect of FR167653 on extended liver resection with ischemia in dogs: Investigation of optimal duration of FR167653 administration and expression of IL-8

Blood and tissue findings in the diagnosis of mesenteric ischaemia: an experimental study.

In this experimental study, after inducing mesenteric ischaemia in dogs, we investigated routine blood biochemistry, serum malondialdehyde (MDA) levels, histopathological changes and tissue MDA levels in the liver and intestines. The study group included 10 dogs. Six dogs which underwent sham operation served as controls. In the study group, the MDA level in liver tissue increased after superior mesenteric artery (SMA) ligation. Various degrees of necrosis were seen in the ileal biopsies 10 hours after the ligation. Hyperaemia and focal necrosis in the liver accompanied the intestinal necrosis if it was limited within the mucosa. However, massive or centrilobular necrosis was observed in the liver of those dogs which had intestinal necrosis that extended into muscular layers. MDA levels in intestinal tissue measured after SMA ligation were significantly higher than the preligation levels. On the other hand, the difference between serum and tissue MDA levels was not significant. The alterations in MDA were not significant in the sham group. Thus it is concluded that the serum MDA levels are valuable markers of diagnosis in intestinal ischaemia.

血行遮断を伴うイヌ拡大肝切除におけるIL-1β・TNF-α の産生阻害剤FR167653の有用性

血行遮断を伴うイヌ拡大肝切除におけるIL-1β・TNF-α の産生阻害剤FR167653の有用性

Characterisation of the canine cardiac sarcolemma in experimental myocardial ischemia

The cardiac sarcolemma was characterized in 13 normal and 11 ischemic dog hearts by enzyme analysis and compositional assays. Significant decreases in the activities of the sodium-potassium and calcium pumps and structural compositional disturbances were observed in ischemia. High concentrations of oleic acid, a fatty acid and palmitoyl carnitine, a fatty acid intermediate caused inhibition of the enzyme pump activities of the normal sarcolemma. Thus, ischemia results in the functional impairment of the sarcolemma. Accumulation of fatty acid and fatty acid intermediates, occurring in myocardial ischemia, could be an underlying mechanism.

Effect of transitory brain ischemia on the synthesis of prostacyclin in arterial hypertension in dogs

Acute and chronic brain ischemia in dogs with rehabilitated hypertension is modeled by applying a tourniquet on the carotid artery. Occlusion of the coronary artery (60 and 120 min for 12 days) induces ischemic stress. Brain ischemia is accompanied by a decrease in plasma prostacyclin and the development of platelet hyperaggregation, which can produce thrombogenesis. The calcium antagonist nifedipine produces stress- and prostacyclin-protective effects by reducing platelet hyperaggregation and preventing thrombogenesis.

Contrast enhanced sonography of visceral perfusion defects in dogs.

The purpose of this study was to assess the utility of an intravenous contrast agent (FS069) for visualization of normal visceral perfusion compared with perfusion after segmental infarction in a canine model. Six mongrel dogs were used as subjects. Splenic, renal, hepatic, and small bowel perfusion was assessed without and with intravenous microbubble contrast material using gray scale, color Doppler, pulsed Doppler, and color power Doppler sonography. Each organ was then reassessed after ligation of a segmental vessel. Imaging was again performed without and with contrast material using all four ultrasonographic modalities. In all organs color and spectral Doppler signals were significantly enhanced from normally perfused tissue after intravenous contrast agent injection. Ischemic areas were more conspicuous after contrast medium injection except in the liver. Hepatic perfusion was maintained by portal flow in the liver despite arterial ligation. Ligation of collateral arcades was required to produce bowel ischemia. Intravenous injection of FS069 improves evaluation of visceral perfusion and identification of focal visceral ischemia in dogs. These results suggest that this agent may increase sensitivity for detection of blood flow in small and deep vessels.

Delayed neuronal death after global incomplete ischemia in dogs is accompanied by changes in phospholipase C protein expression.

Activation of phospholipase C (PLC) increases intracellular Ca2+ and may play a role in delayed neuronal death after ischemia. Because changes in intracellular Ca2+ are believed to participate in ischemic neuronal injury, we tested the hypothesis that PLC beta protein levels are temporally altered in brain regions that undergo neurodegeneration after global incomplete ischemia. Dogs (n = 12) were subjected to 20 minutes of global incomplete ischemia followed by recovery of either 1 (n = 5) or 7 days (n = 7). Six sham-operated animals were used as nonischemic controls. In hematoxylin and eosin-stained brain sections, neuronal density at 1 day after ischemia was unchanged relative to nonischemic controls in hippocampus CA1, caudate, and cerebellar cortex (anterior lobule). However, at 7 days after ischemia, neuronal densities were decreased to 56 +/- 15% (mean +/- SD) and 75 +/- 17% of control in CA1 and caudate, respectively. At 1 and 7 days after ischemia, the percentage of neurons showing ischemic injury increased from 13 +/- 10 to 40 +/- 35% in CA1, 24 +/- 25 to 59 +/- 16% in cerebellum, and 4 +/- 2 to 18 +/- 12% in caudate. Densitometric analysis of immunocytochemically stained brain sections from controls (n = 3). 1 day after ischemia (n = 3), and 7 days after ischemia (n = 5) revealed that PLC beta immunoreactivity was increased in cerebellum at 1 day (0.274 +/- 0.013 v 0.295 +/- 0.005 optical density units [OD] in control and 1 day, respectively) and 7 days (0.108 +/- 0.009 v 0.116 +/- 0.005 O.D. in control and 7 days, respectively). PLC beta immunoreactivity was unchanged after ischemia in caudate and hippocampus. Western blot analysis of PLC beta immunoreactivity in the cerebellar cortex and hippocampus in the control (n = 3), 1 day (n = 2), and 7 days after ischemia (n = 2) groups showed that PLC beta levels were increased after ischemia in cerebellum 266% and 227% above control at 1 and 7 days, respectively. However, in hippocampus, PLC expression after ischemia was unchanged at 97% and 84% of control at 1 and 7 days, respectively. These results show that delayed neuronal degeneration after global incomplete ischemia is accompanied by regional abnormalities in PLC levels. Elevated PLC levels early may represent an aberrant signal transduction mechanism resulting in delayed cell damage, whereas decreased PLC levels later after ischemia may reflect ongoing neurodegeneration.

Extracellular HTK Perfusion and Intracellular Acidification in Ischemic Dog Kidneys

Extracellular HTK Perfusion and Intracellular Acidification in Ischemic Dog Kidneys

Ischemia and reperfusion injury: prevention of pulmonary hypertension and leukosequestration following lower limb ischemia

Ischemia is a common clinical event with potentially serious consequences. The major part of tissue damage occurs upon reperfusion and is mediated by activated neutrophils. Ischemia reperfusion injury is manifested by oedema and increased microvascular permeability. This study tested cardiopulmonary functions following 2 h of lower limb ischemia. Anesthetized dogs were randomized into three groups: nonischemic sham dogs ( n = 4), ischemic control dogs ( n = 8) and ischemic dogs pretreated with prostaglandin (PG)E 1 ( n = 8). In control animals, mean pulmonary artery pressure (mPAP) increased 1 min after declamping from 13.37 ± 2.61 mmHg to 16.88 ± 3.68 mm Hg ( P < 0.05). Pulmonary microvascular pressure (Pmv) increased within 1 minute of reperfusion from 7.71 ± 1.87 mm Hg to 10.54 ± 3.71 mm Hg ( P < 0.05). These changes are consistent with increased lung microvascular permeability. White blood cell count fell slightly but not significantly and lung histology showed leukosequestration in alveoli of 171 ± 22 polymorphonuclear leukocyte (PMN) 10 high powered fields (HPF) in the ischemic control group compared with 121 ± 56 PMN 10 HPF in the sham group ( P < 0.05). Systemic arterial pressure, cardiac output, central venous pressure and pulmonary artery wedge pressure were unaffected. In animals pretreated with PGE 1, mPAP and Pmv were unchanged during reperfusion. Lung histologic findings appeared normal and leukosequestration was not observed. PMN counts in alveoli showed 95 ± 26 PMN 10 HPF , lower than in ischemic control animals ( P < 0.05). These data indicate that lower limb ischemia during reperfusion leads to pulmonary hypertension and leukosequestration. PGE 1 infusion is effective in limiting ischemia reperfusion injury.

Effects of lidocaine and diltiazem on ventricular tachyarrhythmia and dispersion of conduction during severe myocardial ischemia in canine hearts.

The purpose of this study was to investigate the effects of lidocaine and diltiazem on ventricular tachyarrhythmia and dispersion of conduction during severe myocardial ischemia in dogs. Myocardial ischemia was produced by a 10-min occlusion of the left anterior descending artery by the retrograde blood flow technique. Saline, lidocaine, and diltiazem were infused intravenously before and during occlusion in groups A (n = 16), B (n = 22) and C (n = 13), respectively. The incidence of ventricular tachycardia (VT) consisting of ten or more VPC was 19% in group A, 73% in group B and 31% in group C (A vs. B, P < 0.01), and that of ventricular fibrillation (VF) was 31%, 64%, and 15%, respectively (A vs. B, P < 0.05). The time of the onset of VT preceding VF was shorter in group B than in group A (207.9 +/- 13.9 vs. 353.2 +/- 70.7 sec, P < 0.05). The time taken to reach maximal dispersion of conduction delay in the epicardium was shorter in group B than in group A (192.1 +/- 11.9 vs. 337.5 +/- 38.2 sec, P < 0.01), and the dispersion of conduction delay in the intramyocardial layers was smaller in group B than in group A (229.9 +/- 24.5 vs. 360.0 +/- 35.6 sec, P < 0.01). The time taken to reach maximal dispersion of conduction delay in the endocardium was greater in group C than in group A (400.8 +/- 38.8 vs. 274.4 +/- 23.9 sec, P < 0.01). However, there were no significant differences among the three groups with regard to the maximal dispersion of conduction delay in the epicardium, in the endocardium, or intramyocardial layer. These results suggest that lidocaine increased ventricular tachyarrhythmia due to an acute increase in dispersion of conduction in the epicardium and intramural layer, and that diltiazem was not effective in preventing ventricular tachyarrhythmia and did not affect the dispersion of conduction in the epicardium or intramural layer despite improvement in the endocardium.

Comparison of various lazaroid compounds for protection against ischemic liver injury.

Lazaroids are a group of 21-aminosteroids that lack steroid action but have a potent cytoprotective effect by inhibiting iron-dependent lipid peroxidation. However, there have been conflicting reports on the effectiveness and potency of the various lazaroid compounds. In this study, we compared the effectiveness of three major lazaroids on warm liver ischemia in dogs using a 2-hr hepatic vascular exclusion model. The agents were given to the animals intravenously for 30 min before ischemia. The animals were divided into 5 groups: Control (n=10), no treatment; Group F (n=6), U-74006F (10 mg/kg); Group G (n=6), U-74389G (10 mg/kg); Group A1 (n=6), U-74500A (10 mg/kg); Group A2 (n=6), U-74500A (5 mg/kg). The effect of treatment was evaluated by two-week animal survival, hepatic tissue blood flow, liver function tests, blood and tissue biochemistry, and histological analyses. Animal survival in all treated groups was significantly improved compared with the control (83-100% versus 30%). Elevation of liver enzymes after reperfusion was markedly attenuated in treated groups, except for an early significant increase in Group G. Postreperfusion hepatic tissue blood flow was much higher in all treated animals (50% of the preischemic level vs. 25% in the control). Lazaroids, particularly U-74500A at 5 mg/kg (Group A2), suppressed adenine nucleotide degradation during ischemia and enhanced the resynthesis of high-energy phosphates after reperfusion. Although structural abnormalities in postreperfusion liver tissues were markedly ameliorated in all treated groups, Group A2 showed significantly less neutrophil infiltration. Liver injury from warm ischemia and reperfusion was attenuated with all lazaroid compounds, of which U-74500A at 5 mg/kg exhibited the most significant protective activity.

Diabetic chronic hyperglycemia and neurologic outcome following global ischemia in dogs.

We tested the hypothesis that the neuropathologic outcome following recovery from incomplete ischemia is similar in normoglycemia and diabetes. Incomplete global ischemia was induced for 20 min in two groups of dogs: (a) normoglycemic, nondiabetic controls (n = 11) and (b) chronic (3 months), diabetic hyperglycemic subjects (n = 12). Animals were allowed to recover from surgery for 7 days after which they were perfusion-fixed for neuropathology. On paraffin processed tissue stained with hematoxylin and eosin (H&E), ischemic neurons were counted and the per cent of cell damage determined. All control animals survived for 7 days postischemia. Four of 12 diabetic animals survived for 7 days, with the remaining eight diabetic dogs dying within the first 3 days. On day 7, the percentage of neurons showing ischemic cell change in the four diabetic survivors and the 11 nondiabetic controls was similar in the cerebellum, CA1, superior temporal gyrus, and caudate. However, diabetic dogs that did not survive the 7-day recovery period showed cerebellar swelling, reduced Purkinje cell densities, and herniation. During the 3 months prior to ischemia, morning (10.7 +/- 4.4 versus 11.2 +/- 5.2 mM) and afternoon (8.8 +/- 5.0 versus 9.4 +/- 5.3 mM) blood glucose levels in the four surviving and eight nonsurviving diabetic animals, respectively, were similar. However, preischemic blood glucose was significantly elevated in animals that did not survive (7.8 +/- 2.8 versus 15.8 +/- 7.3 mM in survivors and nonsurvivors, respectively). This study shows that diabetic animals surviving 7 days postischemia and nondiabetic controls have similar neuropathology. However, diabetic animals in which glucose control deteriorated during the 24-h prior to ischemia did not survive, possibly due to severe hindbrain edema. These results show that in diabetes, blood glucose control immediately prior to incomplete global brain ischemia is an important determinant of morbidity and neuropathology.

The slowing of ischemic energy demand in preconditioned myocardium.

One or several brief episodes of myocardial ischemia (ischemic preconditioning; IP) rapidly induces tolerance to a later ischemic challenge. This endogenous cardioprotective effect is characterized by a slower onset of cell death. A key feature and probable proximate mechanism of IP is reduced ischemic energy demand which is evident by slower use of ATP and slower accumulation of ischemic catabolites. Several mechanisms for IP and the associated metabolic slowing have been studied: The mitochondrial ATPase is a major cause of ATP hydrolysis in ischemic myocardium but slower ATP depletion in preconditioned myocardium is not due to persistent inhibition of this ATPase. Brief episodes of ischemia in dogs induce stunning as well as IP. Stunning, however, is neither necessary nor sufficient to establish the protective effects of IP. Release of norepinephrine from adrenergic cardiac nerves causes beta adrenergic receptor-mediated stimulation of adenylate cyclase, which stimulates energy-dependent processes. However, IP in dogs that were depleted of catecholamines by pretreatment with reserpine was less effective than IP in control hearts. Thus, an antiadrenergic mechanism does not fully account for the preconditioned state. Another proposed mechanism involves earlier or more complete opening of ATP-sensitive potassium (KATP+) channels. Which of these (or other) pathways mediate the energy sparing effects of ischemic preconditioning remains unknown.

Effect of phospholipid-coated microbubbles (MRX-115) on the detection of testicular ischemia in dogs.

Effect of phospholipid-coated microbubbles (MRX-115) on the detection of testicular ischemia in dogs.

Effects of adenine nucleotide analogues on myocardial dysfunction during reperfusion after ischemia in dogs.

We examined effects of adenine nucleotide on ischemic myocardial stunning in dogs. Pentobarbitalanesthetized open-chest dogs were subjected to 20-min ligation of the left anterior descending coronary artery (LAD), followed by reperfusion for 30 min. Either saline, 5 mM 8-bromo-5'-AMP (tributyryl-AMP), or 30 mM N6, 2', 3'-tributyryl-5'-AMP (tributyryl-AMP), 5 mM 5-amino-4-imidazole carboxamide riboside (AICAr) as a positive reference, was infused at 0.1 ml/kg/min in the left femoral vein throughout the experiment. The myocardial contractile function was measured by ultrasonometry. The tissue levels of high-energy phosphates in the reperfused heart were determined. Myocardial contractile function assessed by % segment shortening (%SS) in the saline-infused group decreased during ischemia and returned toward the preischemic level during reperfusion but incompletely. A significant improvement in the %SS during reperfusion was observed in the 8-bromo-AMP- and AICAr-infused groups but not in the tributyryl-AMP-infused group. The magnitude of the protective effect of the drugs on myocardial contractility during reperfusion was 8-bromo-AMP > AICAr > tributyryl-AMP = saline. Only in the 8-bromo-AMP-infused group were the levels of ATP, ADP, and total adenine nucleotides in the reperfused heart significantly higher than those in the saline-infused group. The present result indicates that 8-bromo-AMP improves the ability of the heart to recover from ischemia and reperfusion associated with a significant restoration of ATP.

Role of nitric oxide in regulation of coronary blood flow during myocardial ischemia in dogs

Objectives. This study was undertaken to examine whether nitric oxide released in ischemic myocardium decreases the coronary vascular resistance and attenuates the severity of contractile and metabolic dysfunction.Background. Endothelium-derived relaxing factor, recently identified as nitric oxide, is a potent relaxant of coronary smooth muscle.Methods. The left anrterior descending coronary artery was perfused through an extracorporeal bypass tube placed in the carotid artery in 56 open chest dogs. After hemodynamic stabilization, we occluded this bypass tube to decrease coronary blood flow to one third of the control flow. Thereafter, we maintained a constant coronary perfusion pressure(40.9 ± 3.1mm Hg).Results. Under ischemic conditions, the coronary arteriovenous differences in nitrate and nitrite (end products of nitric oxide) increased (from 3.5 ± 0.4 [mean ± SEM] to 12.9 ± 2.1 μmol/liter, p < 0.01). n0-Monomethyl l-arginine (3 μg/kg body weight per min, intracoronary) decreased the coronary arteriovenous differences in nitrate and nitrite (5.0 ± 0.9 μmol/liter, p < 0.05) and coronary blood flow (from 29.8 ± 0.5 to 18.1 ± 1.1 ml/100 g per min, p < 0.001). Fractional shortening (from 3.7 ± 1.0 to −1.3 ± 0.7%, p < 0.001) and lactate extraction ration (from −44.0 ± 4.1 to −59.2 ± 4.9%, p < 0.005) of the perfused area also decreased. These values were restored by the concomitant administration of l-arginine. Blood flow to the endomyocardium was decreased relative to the epimyocardium. A reduction in coronary blood flow and worsening of myocardial contractile and metabolic functions due to the administration of nG-monomethyl l-arginine during ischemia were observed in denervated hearts. A reduction in coronary blood flow in ischemic myocardium was observed with the administration of nW-nitro-l-arginene methyl ester as well, although neither nW-nitro-l-arginine methyl ester nor nG-monomethyl l-arginine changed coronary blood flow and myocardial contractile and metabolic functions in the nonischemic myocardium. The cyclic guanosine monophosphate content of epicardial coronary artery increased due to myocardial ischemia; this increased was attenuated with nG-monomethyl l-arginine treatment.Conclusions. We conclude that endogenous nitric oxide predominantly decreases the coronary vascular resistance of ischemic endomyocardium, thereby improving myocardial contractility and metabolic function.

Effect of alkali therapy with NaHCO3 or THAM on cardiac contractility.

We examined the impact of alkali therapy on myocardial contractility in a model of myocardial ischemia in dogs using direct measurements of myocardial contractile function. Myocardial ischemia in the left anterior descending (LAD) artery territory was induced using a perfusion circuit from the internal carotid artery to the LAD artery. Myocardial contractile function was assessed using sonomicrometry for measurement of percent systolic shortening (%SS), preload recruitable stroke work (PRSW) slope, and end-systolic pressure-length relationship (ESPLR) area. Because the blood flow in LAD artery was diminished by approximately 70%, there was a significant decrease in O2 delivery and uptake by the ischemic myocardium. Ischemia led to a significant fall in LAD regional contractile function with %SS decreasing from 15 +/- 2 to 7 +/- 2%, PRSW slope from 82 +/- 10 to 37 +/- 5 mmHg, and ESPLR area from 121 +/- 2 to 48 +/- 14 mmHg.mm (P < 0.05). In six dogs, the intracoronary administration of NaHCO(3) resulted in a significant increase in pH in LAD arterial and venous blood. There was, however, no significant increase in %SS (6 +/- 2), PRSW slope (43 +/- 10 mmHg), or ESPLR area (60 +/- 13 mmHg.mm). Since administration of NaHCO(3) resulted in a significant increase in PCO2 in LAD arterial and venous blood, similar experiments were carried out in five dogs, but with the intracoronary infusion of the amine buffer THAM [tris(hydroxymethyl)aminomethane (Tris) buffer; 2-amino-2-hydroxyl-1,3-propandiol] instead of NaHCO3. Although administration of THAM resulted in a significant increase in pH and a significant decrease in PCO2, in both LAD arterial and venous blood, there was no significant improvement in any of the parameters used to assess myocardial contractile function. In conclusion, administration of alkali (NaHCO3 or THAM) does not enhance the contractile function of the ischemic myocardium.