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K Komamura

Publications and source records attributed to K Komamura.

At least 55 records · Page 3Linked to original sources
PubMed1996

Intracoronary morphology of culprit lesions after reperfusion in acute myocardial infarction: serial angioscopic observations.

OBJECTIVE: This study sought to elucidate the morphologic and pathologic characteristics of culprit lesions in patients with acute myocardial infarction. BACKGROUND: The pathogenic mechanisms of acute myocardial infarction have been discussed on the basis of postmortem histologic examinations. Disruption of lipid-rich plaques is thought to render them thrombogenic. However, the details of coronary morphology have not been elucidated in survivors of myocardial infarction. The quality of angioscopic images has been greatly improved, and clear visualization of the intracoronary milieu can now be obtained. METHODS: Eleven patients with acute myocardial infarction and angiographic demonstration of the culprit lesion were entered into the study. Angioscopic observations were made immediately after reperfusion and at 1-month follow-up. RESULTS: Angioscopic observations were successfully performed in 10 patients immediately after reperfusion and in 10 at 33 +/- 26 (mean +/- SD) days of follow-up. Immediately after reperfusion, red thrombus, white thrombus, yellow plaques and intimal flaps were recognized in 30% (95% confidence interval [CI] 25.7 to 35.7), 100%, 100% and 50% (95% CI 45.0 to 55.0) of patients, respectively. At follow-up, these were recognized in 10% (95% CI 6.6 to 16.4), 60% (95% CI 54.6 to 64.7), 100% and 40% (95% CI 35.3 to 45.4) of patients, respectively. CONCLUSIONS: The thrombus in acute myocardial infarction was always recognized over the yellow plaques. The thrombus formed directly over the plaque was mainly white. Red thrombus might be formed after the blood flow was obstructed by the white thrombus. At approximately 1 month, yellow plaques remained in all patients, and > 50% still had adherent white thrombus.

Aged↗
PubMed1996

Role of activation of protein kinase C in the infarct size-limiting effect of ischemic preconditioning through activation of ecto-5'-nucleotidase.

BACKGROUND: We have reported previously that ischemic preconditioning limits infarct size by increasing ecto-5'-nucleotidase activity. Since we have also reported that protein kinase C activation increases ecto-5'-nucleotidase activity in rat cardiomyocytes, we tested whether activation of protein kinase C during ischemic preconditioning contributes to the infarct size-limiting effect through augmentation of ecto-5'-nucleotidase activity in the canine heart. METHODS AND RESULTS: The coronary artery was occluded four times for 5 minutes with alternating 5-minute periods of reperfusion (ischemic preconditioning). Then the coronary artery was occluded for 90 minutes followed by 6 hours of reperfusion. Infarct size, normalized by the risk area, in the ischemic preconditioning group was smaller than in the control group (42.6 +/- 3.6% in the control group versus 7.9 +/- 1.8% in the ischemic preconditioning group, P < .001). Myocardial ecto-5'-nucleotidase activity was increased after the ischemic preconditioning procedure but the increase in ecto-5'-nucleotidase was attenuated by inhibitors of protein kinase C (polymyxin B and GF109203X). Both polymyxin B and GF109203X blunted the infarct size-limiting effect of ischemic preconditioning (infarct size 33.1 +/- 6.9% and 35.1 +/- 6.4%, respectively). The infarct size-limiting effect was also blunted by an inhibitor of ecto-5'-nucleotidase. Transient administration of methoxamine mimicked the increase in ecto-5'-nucleotidase activity and the infarct size-limiting effect, both of which were abolished by inhibitors of protein kinase C. CONCLUSIONS: We conclude that activation of ecto-5'-nucleotidase and protein kinase C contributes to the infarct size-limiting effect of ischemic preconditioning.

5'-Nucleotidase↗
PubMed1996

Increased release of NO during ischemia reduces myocardial contractility and improves metabolic dysfunction.

BACKGROUND: We have reported that myocardial ischemia increases nitric oxide (NO) production. Several lines of evidence suggest that NO reduces myocardial contraction. Therefore, we tested whether endogenous NO decreases the inotropic response of the ischemic myocardium and whether endogenous NO is beneficial in the metabolic function of ischemic myocardium. METHODS AND RESULTS: The left anterior descending coronary artery was perfused with blood from the left carotid artery in 72 dogs. An infusion of NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NO synthase, did not affect fractional shortening (FS) under nonischemic conditions. After reduction of perfusion pressure so that coronary blood flow decreased to 60% of the control value, FS of the perfused area decreased, and intravenous infusion of isoproterenol increased FS. Before and during intravenous infusion of isoproterenol under conditions of coronary hypoperfusion, FS was significantly increased in the L-NAME group compared with the untreated group. Both lactate extraction ratio and the pH in coronary venous blood were significantly lower in the L-NAME-treated group than in the untreated group during coronary hypoperfusion. Infusion of L-arginine prevented the effects of L-NAME in the ischemic myocardium. CONCLUSIONS: These results indicate that endogenous NO reduces myocardial contractile function and improves myocardial metabolic function in the ischemic heart. The myocardial energy-sparing effect as well as coronary vasodilation due to NO may be beneficial to the ischemic myocardium.

Animals↗
PubMed1996

Activation of ecto-5'-nucleotidase by protein kinase C attenuates irreversible cellular injury due to hypoxia and reoxygenation in rat cardiomyocytes.

Adenosine, synthesized by ecto-5'-nucleotidase, is cardioprotective against ischemia and reperfusion injury. We have previously reported that activation of protein kinase C increases ecto-5'-nucleotidase activity of the rat cardiomyocytes, raising the possibility that activation of protein kinase C protects cardiomyocytes from the irreversible cellular injury via activation of ecto-5'-nucleotidase. To test this hypothesis, cardiomyocytes were isolated from adult male Wistar rats and suspended in modified HEPES-Tyrode buffer solution. The cardiomyocytes were incubated with and without exposure to methoxamine (1 x 10(-6) mol/l) or phorbol 12-myristate 13-acetate (PMA. 1 x 10(-8) mol/l). Ecto-5'-nucleotidase activity increased 15 min after the onset of an exposure to either methoxamine or PMA. Adenosine release during hypoxia and reperfusion was augmented in the methoxamine- and PMA-pretreated cardiomyocytes compared with the untreated cardiomyocytes, which was inhibited by alpha, beta-methyleneadenosine 5'-diphosphate (AOPCP), an inhibitor of ecto-5'-nucleotidase. Irreversible cellular injury assessed by the extent of release of lactate dehydrogenase and the trypan blue exclusion test following 60 min of hypoxia and 60 min of reoxygenation was attenuated in the methoxamine- and PMA-pretreated cardiomyocytes compared with the untreated group, which was also blunted by AOPCP and 8-sulfophenyltheophylline, an adenosine receptor antagonist. An adenosine A1 receptor agonist, N6-cyclohexyladenosine, restored the cardioprotection under the treatment with PMA and AOPCP. We conclude that activation of ecto-5'-nucleotidase via protein kinase C contributes to the attenuation of the irreversible injury of the rat cardiomyocytes due to hypoxia and reoxygenation.

5'-Nucleotidase↗
PubMed1996

Cardioprotection due to preconditioning correlates with increased ecto-5'-nucleotidase activity.

We investigated whether loss of myocardial protection after ischemic preconditioning (IP) is related to the extent of deactivation of activated ecto-5'-nucleotidase. The coronary arteries of mongrel dogs were occluded four times for 5 min separated by 5 min of reperfusion (IP). Five (IP1), 30 (IP2), 60 (IP3), and 120 min (IP4) after the fourth 5-min coronary occlusion or after a corresponding nonischemic period (control groups), the coronary arteries were occluded for 90 min followed by 6 h of reperfusion. The infarct size-limited effect of IP gradually disappeared in the IP2 (21.6 +/- 3.9%) and IP3 (33.8 +/- 3.6%) groups compared with the IP1 group (8.3 +/- 1.6%) and returned to the control level in the IP4 group (39.9 +/- 5.2%). The increased ecto-5' -nucleotidase activity due to the IP procedure decreased according to the order of IP1 to IP4 groups. Infarct size was inversely correlated with ecto-5'-nucleotidase activity (P < 0.001). An inhibitor of ecto-5'-nucleotidase blunted the infarct size-limiting effect of IP. The infarct size-limiting effect of IP decreased as the activation of ecto-5'-nucleotidase was blunted. These results suggest that ecto-5'-nucleotidase activity plays a key role in the cardioprotection of IP.

5'-Nucleotidase↗
PubMed1996

Role of activation of ectosolic 5'-nucleotidase in the cardioprotection mediated by opening of K+c channels.

We tested the hypothesis that the opening of ATP-sensitive K+ channels contributes to activation of ectosolic 5'-nucleotidase and the infarct size-limiting effect of ischemic preconditioning. In open-chest dogs, the left anterior descending coronary artery was occluded four times for 5 min each, separated by a 5-min period of reperfusion (ischemic preconditioning, n = 8). After this procedure, the coronary artery was occluded for 90 min, followed by 6 h of reperfusion. Infarct size was smaller in this group than in the group (control, n = 8) with a 45 min interval instead of the ischemic preconditioning procedure (40.1 +/- 3.9 vs. 6.4 +/- 1.9%). Glibenclamide blunted the infarct size-limiting effect of ischemic preconditioning (infarct size, 37.3 +/- 5.8%; n = 7), and transient exposures to cromakalim and nicorandil mimicked it [infarct size, 10.1 +/- 3.1 (n = 7) and 11.1 +/- 2.7% (n = 8), respectively]. Ectosolic and cytosolic 5'-nucleotidase activity increased in the ischemic preconditioning group compared with that in the control group; this preconditioning-induced increase in 5'-nucleotidase activity was blunted by glibenclamide (n = 5) and mimicked by cromakalim (n = 5) and nicorandil (n = 5). The infarct size-limiting effect due to cromakalim and nicorandil was blunted by alpha,beta-methyleneadenosine 5'-diphosphate, an inhibitor of ectosolic 5'-nucleotidase [infarct size, 37.7 +/- 5.6 (n = 9) and 36.8 +/- 4.8% (n = 7), respectively] and 8-sulfophenyltheophylline (infarct size with cromakalim, 44.7 +/- 4.6%; n = 7). We conclude that activation of ectosolic 5'-nucleotidase due to the openers of ATP-sensitive K+ channels contributes to the infarct size- limiting effect of ischemic preconditioning.

5'-Nucleotidase↗
PubMed1995

Beneficial effects of inhibition of angiotensin-converting enzyme on ischemic myocardium during coronary hypoperfusion in dogs.

BACKGROUND: Angiotensin-converting enzyme (ACE) produces angiotensin II, causing vasoconstriction of coronary arteries and reduction of coronary blood flow. The present study was undertaken to test the hypothesis that an ACE inhibitor increases coronary blood flow and improves myocardial metabolic and contractile functions of ischemic myocardium. METHODS AND RESULTS: In 65 open-chest dogs, the left anterior descending coronary artery was perfused through an extracorporeal bypass tube from the left carotid artery. When cilazaprilat (3 micrograms/kg per minute) was infused into the bypass tube for 10 minutes after reduction of coronary blood flow due to partial occlusion of the bypass tube, coronary blood flow increased from 30 +/- 1 to 43 +/- 2 mL/100 g per minute despite there being no changes in coronary perfusion pressure (43 +/- 1 mm Hg). The ratio of myocardial endocardial flow to epicardial flow increased during an infusion of cilazaprilat. Both fractional shortening and lactate extraction ratio of the perfused area were increased (fractional shortening: 4.1 +/- 0.6% to 8.9 +/- 0.6%, P < .001; lactate extraction ratio: -55.7 +/- 3.3% to -36.7 +/- 3.9%, P < .001). During an infusion of cilazaprilat, the bradykinin concentration of coronary venous blood was markedly increased. The increased coronary blood flow due to cilazaprilat was attenuated by HOE-140 (an inhibitor of bradykinin receptors; coronary blood flow: 35 +/- 2 mL/100 g per minute), and by N omega-nitro-L-arginine methyl ester (an inhibitor of nitric oxide synthase; coronary blood flow: 34 +/- 2 mL/100 g per minute). Intracoronary administration of bradykinin mimicked the beneficial effects of cilazaprilat. Cyclic GMP content of the coronary artery was increased by cilazaprilat compared with the untreated condition in the ischemic myocardium. In the denervated hearts, the increased coronary blood flow due to cilazaprilat was not attenuated. On the other hand, CV11974, an inhibitor of angiotensin II receptors, slightly increased coronary blood flow to 34 +/- 2 from 30 +/- 1 mL/100 g per minute. CONCLUSIONS: We conclude that an inhibitor of ACE can increase coronary blood flow and ameliorate myocardial ischemia, primarily due to accumulation of bradykinin and production of nitric oxide from the ischemic myocardium. Inhibition of angiotensin II production due to inhibition of ACE partially contributes to coronary vasodilation in the ischemic myocardium.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1995

Roles of alpha 1-adrenoceptor activity in the release of nitric oxide during ischemia of the canine heart.

The difference in end-products of the nitric oxide, i.e., nitrate-plus-nitrite, in the coronary arterial and venous blood was increased during coronary hypoperfusion of the canine heart (12.8 +/- 0.6 vs. 2.2 +/- 0.2 microM at the baseline). Norepinephrine from sympathetic nerve endings in the heart is released due to ischemic stress, however the relation of norepinephrine with nitric oxide is unknown during ischemia. Neither beta- or alpha 2-adrenoceptor antagonists attenuated the release of nitric oxide during coronary hypoperfusion. An intracoronary infusion of an alpha 1-adrenoceptor antagonist attenuated the release of nitric oxide during coronary hypoperfusion (5.3 +/- 0.4 microM), and the attenuation of alpha 1-adrenoceptor activity further decreased coronary blood flow during hypoperfusion. These findings suggest that alpha 1-adrenoceptor activity contributes to the mechanisms whereby nitric oxide is released from the ischemic myocardium.

Animals↗
PubMed1995

Plasma nitric oxide end products are increased in the ischemic canine heart.

Coronary arteriovenous difference in stable end-products of nitric oxide metabolism, nitrate and nitrite, was increased in ischemic canine hearts. In accordance with the reduction of coronary blood flow by 40, 67, 80 and 100%, the plasma nitrate+nitrite concentration increased from 3.2 +/- 0.6 to 8.7 +/- 1.3, 12.5 +/- 1.8, 15.9 +/- 2.7, and 20.2 +/- 2.3 microM, respectively. The plasma nitrate+nitrite concentrations were further elevated during reperfusion. Administration of NG-nitro-L-arginine methyl ester decreased the production of both nitrate+nitrite and coronary blood flow; the former was restored by the concomitant administration of L-arginine. These findings suggest that the increases in the nitric oxide production result from the action of nitric oxide synthase during myocardial ischemia and reperfusion, decreasing coronary vascular resistance and attenuating myocardial ischemia.

Animals↗
PubMed1995

Alpha 1-adrenoceptor activation increases ecto-5'-nucleotidase activity and adenosine release in rat cardiomyocytes by activating protein kinase C.

BACKGROUND: Adenosine is an important regulator of many cardiac functions and is synthesized primarily by ecto- and cytosolic 5'-nucleotidase. We have previously reported that alpha 1-adrenoceptor blockade attenuates adenosine release from ischemic myocardium, raising the possibility that alpha 1-adrenoceptor activation activates 5'-nucleotidase. This study tested whether activation of protein kinase C by alpha 1-adrenoceptor activation increases 5'-nucleotidase activity and augments adenosine release. METHODS AND RESULTS: Cardiomyocytes were isolated from adult male Wistar rats and suspended in modified HEPES-Tyrode's buffer solution. After stabilization, the cardiomyocytes were incubated with and without an exposure to norepinephrine (10(-9) to 10(-5) mol/L) while being treated with propranolol and yohimbine or with and without an exposure to methoxamine (10(-9) to 10(-5) mol/L). Ecto-5'-nucleotidase activity was increased by norepinephrine and methoxamine during 30 minutes in a dose-dependent manner, whereas cytosolic 5'-nucleotidase was not activated. These increases in ecto-5'-nucleotidase activity were inhibited by GF109203X, an inhibitor of protein kinase C, and mimicked by phorbol 12-myristate 13-acetate (PMA), an activator of protein kinase C. The increase in ecto-5'-nucleotidase was not prevented by cycloheximide. When ecto-5'-nucleotidase activity increased, adenosine release was augmented in methoxamine- and PMA-treated cardiomyocytes (1299 +/- 252% and 1372 +/- 149%, respectively) compared with the untreated group (578 +/- 26%). The increase in adenosine release was blunted by GF109203X and alpha, beta-methyleneadenosine 5'-diphosphate, an inhibitor of ecto-5'-nucleotidase. CONCLUSIONS: Thus, we conclude that alpha 1-adrenoceptor-mediated increases in ecto-5'-nucleotidase activity are attributed to activation of protein kinase C in rat cardiomyocytes.

5'-Nucleotidase↗
PubMed1995

Evidence for nitric oxide generation in the cardiomyocytes: its augmentation by hypoxia.

Recent reports suggest that endothelial-dependent relaxant factor, recognized as nitric oxide (NO), reduces myocardial contractility. Here, we showed that both exposures to acetylcholine and bradykinin for 30 min increased cyclic guanylate monophosphate (cyclic GMP) in isolated rat cardiomyocytes. These increases in cyclic GMP were blunted by NW-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NO synthase. Hypoxia augmented the cyclic GMP accumulation due to exposures to acetylcholine and bradykinin, which were blunted by L-NAME. The increases in cyclic GMP due to acetylcholine and bradykinin during normoxic and hypoxic conditions were not blunted by aminoguanidine, an inhibitor of inducible NO synthase. These findings revealed that NO is produced in cardiomyocytes due to stimulation of NO synthase and modulates their own guanylate cyclase, which was augmented by hypoxia. NO production, through NO synthase in cardiomyocytes, may constitute autocrine regulations of myocardial contractility and paracrine regulations of coronary vasodilation and platelet aggregation.

Acetylcholine↗
PubMed1995

Elastic recoil and intimal thickening after coronary stenting.

In this study, the long-term elastic recoil of the stents and the intimal thickening over the stents were evaluated separately. Twenty-nine patients who received a Wiktor coronary stent were angiographically followed-up at 2 weeks, 3 months, and 6 months. The elastic recoil of the stent was evaluated by the changes in minimum stent diameter. The intimal thickness was evaluated by the difference between minimum stent diameter and minimum lumen diameter. Minimum stent diameter showed no significant change up to 6 months. The significant increase (P < 0.05) of the intimal thickness was detected only between 2 weeks and 3 months. In conclusion, the Wiktor stent prevented the elastic recoil up to 6 months, and was covered by the neointima which increased its thickness mainly between 2 weeks and 3 months after stenting. It was suggested that stent restenosis was not caused by the elastic recoil, but by the intimal thickening.

Aged↗
PubMed1995

Activation of protein kinase C increases adenosine production in the hypoxic canine coronary artery through the extracellular pathway.

Both ischemia and hypoxia increase adenosine production in the heart. This study tested whether hypoxia increases adenosine production in the coronary artery via ecto-5'-nucleotidase and the role of protein kinase C in this condition. Canine left circumflex coronary artery was rapidly removed and incubated in 10 mL Krebs-Henseleit solution for 30 minutes. The Krebs-Henseleit solution contained 5'-iodotubercidin and 2'-deoxycoformycin, which inhibit adenosine kinase and adenosine deaminase, respectively. Adenosine production was measured in intact coronary arteries under normoxic conditions (16.2 +/- 1.2 pmol/mg protein). Adenosine production was reduced by 27% after removal of endothelium. Ecto-5'-nucleotidase activity of coronary arteries with and without endothelium was 51 +/- 6 and 41 +/- 4 nmol/mg protein per minute under normoxic conditions. Hypoxia increased adenosine production to 27.0 +/- 2.3 and 20.0 +/- 0.8 pmol/mg protein with and without endothelium. Hypoxia also increased ecto-5'-nucleotidase activity of coronary arteries with and without endothelium (74 +/- 8 and 53 +/- 5 nmol/mg protein per minute; P < .05). Increases in adenosine production under hypoxic conditions were blunted by both an inhibitor of ecto-5'-nucleotidase and inhibitors of protein kinase C. Activation of ecto-5'-nucleotidase was blunted by an inhibitor of protein kinase C. These results indicate that hypoxia increased extracellular adenosine production and activated ecto-5'-nucleotidase via activation of protein kinase C in coronary arterial smooth muscle and endothelial cells. Increased adenosine production in coronary arteries during hypoxia may contribute to coronary vasodilation and cardioprotection against ischemic injury.

5'-Nucleotidase↗
PubMed1994

Progressive decreases in coronary vein flow during reperfusion in acute myocardial infarction: clinical documentation of the no reflow phenomenon after successful thrombolysis.

OBJECTIVES: This study was undertaken to examine the effects of coronary flow dynamics after thrombolysis on infarct size limitation. BACKGROUND: It has been commonly accepted that early thrombolysis does not necessarily salvage infarcted myocardium. Plausible causes for myocardial necrosis include such factors as elapsed time to reperfusion, residual stenosis, collateral vessels, hemodynamic loads, preconditioning and reperfusion injury. Recently, the no reflow phenomenon has been elucidated to be associated with infarct extension in clinical studies employing contrast echocardiography or thallium scintigraphy. METHODS: Nineteen patients with early reperfusion in acute anterior myocardial infarction and comparable clinical background were studied. The patients were classified into two groups on the basis of pattern of thermodilution measurements of great cardiac vein flow after reperfusion: group A, 9 patients with a progressive decrease in great cardiac vein flow during the 1st 24 h of the onset of infarction; and group B, 10 patients without this observation. Left ventricular ejection fraction and thallium perfusion defect were compared between the two groups at follow-up. RESULTS: There were no significant differences in systemic hemodynamic variables between groups A and B, and neither group had recurrent ischemic events suggesting reocclusion or restenosis during the study. In group A, both great cardiac vein flow (mean +/- SD 44 +/- 17% reduction) and oxygen extraction (38 +/- 15% reduction) were progressively decreased after the onset of reperfusion. Compared with group B, this group showed a lower left ventricular ejection fraction (36 +/- 7% vs. 63 +/- 15%, p < 0.01) and a larger thallium-201 defect severity index (1,091 +/- 366 U vs. 247 +/- 261 U, p < 0.01) at follow-up. Although other patient characteristics were comparable between the two groups, antecedent angina occurred in 90% of group B patients in contrast to only 33% of group A patients. CONCLUSIONS: Salvage of myocardium from infarction by successful thrombolysis was not observed in the patients demonstrating progressive decreases in great cardiac vein flow (group A). In those patients, inadequate myocardial reperfusion on a microvascular basis might be associated with a much larger myocardial infarction. Antecedent angina may protect against a progressive decrease in coronary flow and may have beneficial effects on infarct size limitation.

Adult↗
PubMed1994

Neointimal coverage of stents in human coronary arteries observed by angioscopy.

OBJECTIVES: The aim of this study was to reveal the time course of the neointimal coverage of stents placed in the human coronary arteries. BACKGROUND: In deciding the protocol of anticoagulant and antiplatelet therapy for patients who undergo stent implantation, the condition of the neointimal coverage of stents should be taken into consideration. However, the time course of the neointimal coverage of stents has not been elucidated in human coronary arteries. METHODS: Serial angioscopic observations were performed immediately after stenting, at 8 to 45 days (short-term follow-up) and at 65 to 142 days (long-term follow-up) in patients who underwent implantation of the Wiktor coronary stent in the restenotic lesion or in the lesion of acute or threatened closure after balloon angioplasty. RESULTS: Angioscopic observations were successfully performed in 14 cases immediately after stenting, in 11 cases at short-term follow-up and in 13 cases at long-term follow-up. Immediately after stenting and even at 8 to 18 days after stenting, the stent was not covered by the neointimal layer in any case. However, at 65 to 142 days after stenting, the stent was covered by the neointimal layer in all cases. Angioscopically, three types of neointimal layer were recognized: a white layer with a cottonlike surface in three cases, a white layer with a smooth surface in eight cases and a transparent layer with a smooth surface in two cases. CONCLUSIONS: Although some experimental results in animals have shown completion of neointimal coverage of stents in a few weeks, in this serial angioscopic follow-up study, the completion of neointimal coverage of stents in human coronary arteries required approximately 3 months.

Angioscopy↗
PubMed1994

Effects of anaesthesia and recent surgery on diastolic function.

OBJECTIVE: The aims were to determine the effects and the extent to which halothane anaesthesia affects diastolic function both immediately after and remote from surgery and to investigate whether the effect is due to alterations in loading conditions. METHODS: Eight mongrel dogs were studied under halothane anaesthesia (0.5-1.5 end tidal vol%) with the chest closed, after acute instrumentation with left ventricular pressure transducers, left atrial and aortic catheters, and left ventricular diameter and wall thickness crystals. The same dogs were then studied in the fully conscious state, 2-3 weeks later. An additional four dogs were studied in the conscious state and then again under halothane anaesthesia remote from acute instrumentation. The left ventricular isovolumetric relaxation time constant, tau, as well as myocardial and chamber stiffness constants were used as indices of diastolic function. RESULTS: Following halothane anaesthesia and recent surgery, tau was prolonged significantly compared to the conscious state, at 30(SEM 1) v 22(1) ms (p < 0.01), but there were no changes in either myocardial or chamber stiffness. While tau remained sensitive to increased heart rate and enhanced contractility and was prolonged by increasing afterload in both the anaesthetised and conscious states, it was consistently prolonged following halothane anaesthesia and recent surgery even at matched levels of contractile states, heart rates and loading conditions, compared to the conscious state, at 26(1) v 19(1) ms (p < 0.01). When the effects of halothane anaesthesia were examined after full recovery from surgery, tau was still prolonged under halothane anaesthesia, at 29(2) v 20(1) ms (p < 0.01), compared to the conscious state, but in contrast to the findings following halothane anaesthesia and recent surgery, it was fully normalised [19(1) v 19(1) ms] when contractile state and loading conditions were matched. CONCLUSIONS: Left ventricular diastolic function is influenced markedly by halothane anaesthesia and recent surgery, and to a degree comparable to many pathological states. The effects of halothane anaesthesia and recent surgery appear to prolong the isovolumetric relaxation time constant independently of heart rate, contractility, and loading conditions and are most likely to be due to the combined direct effects of anaesthetics and acute instrumentation.

Anesthesia, Inhalation↗
PubMed1994

Left ventricular systolic dysfunction precedes diastolic dysfunction during myocardial ischemia in conscious dogs.

We studied the initial effects of regional and global left ventricular (LV) ischemia induced by left circumflex and left main coronary artery occlusion (CAO), respectively, on indexes of systolic and diastolic LV function in conscious dogs to determine whether diastolic abnormalities precede systolic dysfunction or vice versa during the onset of either regional or global myocardial ischemia. With regional myocardial ischemia, within four beats after left circumflex CAO, there was a significant decrease in end-systolic wall thickness in the ischemic zone followed by significantly enhanced postsystolic wall thickening in the nonischemic zone at beat 6. Both peak negative first derivative of left ventricular pressure (LV dP/dt) and the isovolumic relaxation half-time (T 1/2) were prolonged, but later (i.e., by the 9th beat). During sustained CAO T1/2 was normalized shortly after postsystolic thickening in the nonischemic zone had disappeared despite persistent regional systolic asynchrony and shortened ejection time. Thus postsystolic thickening in the nonischemic zone played a major role in the early, transient changes in isovolumic relaxation after acute induction of regional ischemia. With global myocardial ischemia, induced by left main coronary occlusion, indexes of systolic function (e.g., LV dP/dt, ejection fraction, and velocity of circumferential endocardial fiber shortening) were also depressed significantly before (by 5-15 beats) indexes of LV diastolic function [e.g., time constant of isovolumic relaxation and LV myocardial and chamber stiffness (by 35-45 beats)]. Similar results were observed in the presence of autonomic blockade, when heart rate did not change with CAO. Thus, during the induction of either acute regional or acute global LV ischemia in conscious dogs, LV systolic dysfunction occurs before diastolic dysfunction.

Animals↗