Effects of bretylium tosylate on inhomogeneity of refractoriness and ventricular fibrillation threshold in canine hearts with quinidine-induced long QT interval

We studied effects of bretylium tosylate (6 mg X kg-1, injected intravenously over 60s) on ventricular refractoriness and its inhomogeneity, and ventricular fibrillation threshold (VFT) in canine hearts with quinidine-induced long QT interval. In 3 anaesthetised open chest dogs, 30 mg X kg-1 of quinidine sulphate was injected intravenously over 5 min to produce QT prolongation. Effective refractory period (ERP) was determined at 8 test points of the right ventricle using extrastimuli. Temporal dispersion as an expression of inhomogeneity of ventricular refractoriness was estimated as the difference between the longest and the shortest ERP. VFT was determined using a train of pulses, 4 ms in duration and at 10 ms intervals. Effects of bretylium were determined from 30 to 60 min after injection. Quinidine-induced long QT interval did not change after bretylium (358 +/- 37 vs 348 +/- 26 ms) when transiently elevated blood pressure returned to the pre-bretylium level. Bretylium shortened ERP slightly (278 +/- 16 vs 268 +/- 14 ms, p less than 0.02) but did not shorten ERP after premature depolarisation (209 +/- 14 vs 209 +/- 15). However, temporal dispersion was significantly decreased by bretylium. VFT, which was lowered by quinidine (14.5 +/- 5.0 vs 8.5 +/- 2.9 mA, p less than 0.01), was elevated significantly by bretylium (21.9 +/- 6.9, p less than 0.001). These effects of bretylium might be attributed to the combination of its direct electrophysiology and indirect adrenergic actions.     

Effects of chronic hypokalemia on ventricular vulnerability during acute myocardial ischemia in the dog

Chronic hypokalemia (2.9 +/- 0.2 mEq/L) was induced in 10 dogs by a low potassium diet and furosemide administration. Five control dogs with normokalemia (5.0 +/- 0.3 mEq/L) were fed an ordinary diet. Three of the 10 hypokalemic dogs had electrically induced, nonsustained ventricular tachycardia (NSVT) and ventricular fibrillation (VF); none of the 5 control dogs had these ventricular arrhythmias. After ligation of the left anterior descending coronary artery (LAD), 4 of the 10 hypokalemic dogs developed spontaneous VF and 6 had electrically induced NSVT and VF, whereas 2 of the 5 control dogs had only NSVT. The effective refractory period (ERP) of the ventricles of the hypokalemic dogs was slightly longer than that of the control dogs. After LAD ligation, only the ERP of the anterior wall of the left ventricle was prolonged significantly in either group (p less than 0.01). The ventricular fibrillation threshold (VFT) of hypokalemic dogs was significantly lower than the control dogs (p less than 0.05), and was reduced markedly (p less than 0.05) after LAD ligation. A positive correlation between VFT and serum potassium level was observed. Thus, chronic hypokalemia increases ventricular vulnerability. This effect depends upon the severity of hypokalemia and is markedly augmented by acute myocardial ischemia. These findings indicate that, in clinical settings, preexisting hypokalemia and its severity may play important roles in the occurrence of lethal ventricular arrhythmias during the acute phase of myocardial infarction.     

Mechanism of antiarrhythmic action of beta-blocking agents

We investigated the antiarrhythmic effect of beta-blocking agents. Using 35 anesthetized dogs, the chest was opened and the left anterior descending coronary artery (LAD) was ligated for 30 min and the ventricular multiple response threshold (VMRT) was observed in the time course. The dogs were divided into five groups premedicated intravenously ten min before LAD ligation with either isotonic saline (the control group), D,L-propranolol (0.5 mg/kg), D-propranolol (0.5 mg/kg), D,L-pindolol (0.1 mg/kg), or D,L-acebutolol (2.5 mg/kg). Thirty min after ligation, myocardial mitochondria were prepared from the ischemic and the non-ischemic areas, and then the content of mitochondrial long-chain acyl-CoA and Ca++-binding activity were measured. The value of VMRT 1.59 +/- 0.21 mA before ligation decreased to 0.99 +/- 0.13 mA 30 min after ligation. Content of acyl-CoA in mitochondria from the ischemic area increased significantly compared to those from the non-ischemic area. Mitochondrial Ca++-binding activity in the ischemic area decreased significantly compared to that in the non-ischemic area. Each administration of three beta-blocking agents prevented the decreases in VMRT and Ca++-binding activity and excessive accumulation of acyl-CoA; D-propranolol had no effect. These results suggest that the antiarrhythmic action of beta-blocking agents is based, at least in part, on the protection from decrease in Ca++-binding activity due to mitochondrial dysfunction induced by the excessive accumulation of long-chain acyl-CoA in mitochondria.     

Antidysrhythmic actions of meobentine sulfate

The antiarrhythmic efficacy of meobentine sulfate, a bethanidine derivative lacking inhibitory effects on adrenergic neuronal function, was assessed in three canine models. Intravenous meobentine sulfate, administered in dosages of 5.0, 10,0, and 20.0 mg/kg, produced a dose-related increase in the ventricular fibrillation threshold (VFT) under nonischemic conditions (7.6 +/- 1.8 mA vs 37.8 +/- 8.6 mA) (20 mg/kg; p less than 0.05) and during regional myocardial ischemia (5.6 +/- 1.5 mA vs 41.8 +/- 9.1 mA) (20 mg/kg; p less than 0.05). The VFT was also increased in the presence of chronic ischemic injury (6.4 +/- 1 mA to 31 +/- 10 mA) (20 mg/kg; p 0.05). In the conscious dog, 4 days after an anterior myocardial infarction, programmed electrical stimulation (PES) produced nonsustained ventricular tachycardia (VT) in five dogs. After meobentine sulfate administration, eight of nine animals had sustained VT and one animal developed ventricular fibrillation (VF). At a dose of 20 mg/kg, there was prolongation of the cycle length of the VT (169 +/- 11 msec to 237 +/- 20 msec), prolongation of the QRS duration (58 +/- 2.6 msec to 71 +/- 3.7 msec), and prolongation of the delay in epicardial activation. There was an enhanced potential after meobentine administration for programmed stimulation to produce ventricular arrhythmias with the introduction of fewer premature impulses. In the third canine model, conscious dogs with a previous anterior myocardial infarction developed VF in response to electrically induced left circumflex coronary artery injury. Meobentine (20 mg/kg) failed to prevent VF in eight of eight dogs. These results suggest that while meobentine sulfate significantly increases the electrical VFT, it does not protect the conscious canine from the induction of ventricular tachyarrhythmias in response to PES, and it does not prevent VF in a conscious canine model of sudden coronary death.(ABSTRACT TRUNCATED AT 250 WORDS)     

大鼠心肌梗死后梗死周边区Sema 3A的变化及其对心室颤动阈值的影响

目的研究心肌梗死(简称心梗)后大鼠心脏Sema 3A及其受体neuropilin-1(NP-1)和电生理的变化。方法50只大鼠随机分为心梗组(n=30)和假手术组(n=20)。用结扎左冠状动脉前降支的方法制备大鼠心梗模型。8周后,测定大鼠梗死周边区心室颤动(简称室颤)阈值和有效不应期;应用蛋白质印迹法和逆转录聚合酶链反应技术检测梗死周边区Sema 3A及其受体的蛋白和mRNA的表达。结果心梗后8周,大鼠梗死周边区心肌室颤阈值降低(7.1±4.1 V vs 13.0±2.1 V,P<0.05),有效不应期延长(76±9 ms vs 61±8 ms,P<0.05)。大鼠心脏梗死周边区Sema 3A蛋白和mRNA的相对值都显著的降低。但是,Sema 3A的受体蛋白和mRNA的相对值都明显的升高。结论心梗后大鼠心脏梗死周边区发生电重构;梗死周边区Sema 3A明显减少,Sema 3A的受体明显增加。     

The efficacy of intermittent coronary sinus occlusion in the absence of coronary artery collaterals

The purpose of this study was to evaluate the efficacy of time-controlled intermittent coronary sinus occlusion (ICSO) in preserving regional and global mechanical function during acute ischemia in an animal preparation without significant arterial collateral vessels. Seventeen (eight control, nine ICSO) swine heart preparations undergoing extracorporeal coronary perfusion in situ were subjected to ligation of the left anterior descending coronary artery (LAD) distal to the first major diagonal branch. Data were obtained before and immediately after coronary artery ligation in both animal groups. ICSO, 15 sec of occlusion alternating with 5 sec of release, was then begun in the treatment group. Additional data were obtained in both control and treatment groups at 15 min intervals for 1 hr starting immediately after coronary artery ligation. Global left ventricular function was assessed by shifts in left ventricular end-diastolic pressure and left ventricular dP/dt with left ventricular systolic pressure maintained at about 100 mm Hg. Regional mechanical function was evaluated with transmurally placed ultrasonic crystals. Pressure was also measured directly in the coronary sinus and LAD distal to the ligature. Regional myocardial blood flow was measured in the ischemic bed using 9 micron diameter radiolabeled microspheres injected before, immediately after, and 60 min after coronary artery ligation in both treated and control animals. LAD mean pressure measured distal to the ligation (less than 16 mm Hg) and ischemic bed myocardial blood flow (less than 0.01 ml/g/min) confirmed the absence of significant arterial-arterial collaterals in this preparation. Mean coronary sinus pressure increased significantly (p less than .001) in treated animals during ICSO (e.g., 11.2 +/- 1.6 to 66.2 +/- 10.0 mm Hg at 15 min after coronary ligation). Mean LAD pressure distal to the coronary ligature also increased during ICSO (14.2 +/- 1.2 to 26.8 +/- 1.6 mm Hg), with a similar but delayed rate of pressure rise. No significant differences in left ventricular end-diastolic pressure or left ventricular dP/dt were noted between control or treated animals after coronary ligation. Ischemic bed systolic wall thickening, present before coronary ligation, was not present after occlusion and was not improved during intermittent coronary sinus occlusion in the treatment group. We conclude that in an animal preparation without significant collateral circulation, intermittent coronary sinus occlusion is incapable of restoring regional or global left ventricular mechanical function during conditions of acute ischemia.     

Autonomic modulation of electrical restitution, alternans and ventricular fibrillation initiation in the isolated heart

OBJECTIVE: Abnormal autonomic nerve activity is a strong prognostic marker for ventricular arrhythmias but the mechanisms underlying the autonomic modulation of ventricular fibrillation (VF) initiation are poorly understood. We examined the effects of direct sympathetic (SS) and vagus (VS) nerve stimulation on electrical restitution, alternans and VF threshold (VFT) in a novel isolated rabbit heart preparation with intact dual autonomic innervation. METHODS: Monophasic Action Potentials (MAPs) were recorded from a left ventricular epicardial site on innervated, isolated rabbit hearts (n=16). Standard restitution, effective refractory period (ERP), electrical alternans and VFT were measured at baseline and during SS and VS separately. RESULTS: The restitution curve was shifted downwards and made steeper with SS whilst VS caused an upward shift and a flattening of the curve. The maximum slope of restitution was increased from 1.30+/-0.10 at baseline to 1.86+/-0.17 (by 45+/-12%, P<0.01) with SS and decreased to 0.69+/-0.10 (by 51+/-6%, P<0.001) with VS. ERP was decreased from 127.3+/-2.5 ms to 111.8+/-1.8 ms with SS (by 12+/-2%, P<0.001) and increased to 144.0+/-2.2 ms with VS (by 13+/-2%, P<0.001). VFT was decreased from 4.7+/-0.6 mA to 1.9+/-0.5 mA with SS (by 64+/-5%, P<0.001) and increased to 8.7+/-1.1 mA with VS (by 89+/-14%, P<0.0005). There was a significant inverse relationship between the maximum slope of restitution and VFT (r=-0.63, P<0.0001). When compared with baseline, SS caused electrical alternans at longer pacing cycle lengths (139.0+/-8.4 vs. 123.0+/-7.8 ms, P<0.01) with greater degree of alternans (32.5+/-9.9 vs. 15.4+/-3.2%, P<0.05). It also caused a wider range of cycle lengths where alternans occurred (53.0+/-6.2 vs. 41.0+/-7.0 ms, P<0.05) whilst vagus nerve stimulation shortened this range (33.0+/-7.3 ms, P<0.001). CONCLUSIONS: Sympathetic stimulation increased maximum slope of restitution and electrical alternans but decreased ERP and VF threshold whilst vagus nerve stimulation had opposite effects. The interaction between action potential duration and beat-to-beat interval may play an important role in the autonomic modulation of VF initiation.     

Early autonomic and repolarization abnormalities contribute to lethal arrhythmias in chronic ischemic heart failure: characteristics of a novel heart failure model in dogs with postmyocardial infarction left ventricular dysfunction

OBJECTIVES: Using a model of arrhythmias associated with ischemic left ventricular (LV) dysfunction, this study investigated autonomic and electrophysiologic mechanisms associated with sudden cardiac death (SCD) in chronic heart failure (HF). BACKGROUND: Left ventricular dysfunction from ischemic heart disease is associated with many instances of SCD. Electrophysiologic and autonomic derangements occur in HF, but their contribution to SCD risk is poorly understood. METHODS: Sudden death risk was assessed in 15 dogs with a healed anterior myocardial infarction (MI) during submaximal exercise and brief acute circumflex ischemia. Left ventricular dysfunction was then induced by repetitive circumflex microembolization until LV ejection fraction reached 35%. Before embolization, six dogs were susceptible to SCD, and nine were resistant. RESULTS: Baroreflex sensitivity was lower in susceptible dogs (10 ms/mm Hg +/- 4 ms/mm Hg vs. 20 ms/mm Hg +/- 11 ms/mm Hg, p = 0.04). QT intervals from susceptible dogs were longer after MI (246 ms +/- 26 ms susceptible vs. 231 ms +/- 20 ms resistant, p < 0.001) and prolonged within eight weeks after LV dysfunction was established (from 246 ms +/- 26 ms to 274 ms +/- 56 ms, +11%, p < 0.01). Heart rate in susceptible dogs increased during transient ischemia (+20%) and with progressive LV dysfunction (102 beats/min +/- 28 beats/min baseline to 154 beats/min +/- 7 beats/min LV dysfunction, p = 0.003). All susceptible dogs had spontaneous sustained ventricular tachycardia culminating in SCD. In contrast, QT intervals in resistant dogs prolonged after 24 +/- 6 weeks (from 231 ms +/- 20 ms to 238 ms +/- 15 ms, p < 0.05), and heart rates were unchanged. Only one resistant dog died suddenly with LV dysfunction. CONCLUSIONS: Depressed vagal and elevated sympathetic control of heart rate coupled with abnormal repolarization are associated with high SCD risk when post-MI LV dysfunction develops.     

Effects of captopril on regional segment motion during acute coronary occlusion.

The effects of captopril on myocardial segment function in different degrees of transient coronary occlusion were studied using ultrasonic dimension gauges in 15 open-chest dogs. The occlusion procedures (OP) were performed on the left anterior descending coronary artery (LAD) in eight dogs and on the left circumflex coronary artery (Cx) in seven dogs. To measure the changes in segment shortening in the subendocardium we used eight dogs (ischemic and control zones: four dogs LAD and four dogs Cx). To measure the changes in wall thickening we used seven dogs (ischemic and control zones: three dogs LAD and four dogs Cx). Total coronary OP lasting 1 min and partial OP (70-80%) lasting 1 min and 2 min 30 s, before and after captopril (0.25 mg/kg i.v.) were performed. Left ventricular pressure, dP/dt, coronary flow, and ECG were monitored. Total coronary OP (1 min) changed segment shortening (18% LAD; 14% Cx) and wall thickening (19% LAD; 18% Cx) to values of dyskinesis (-3% and -4% for shortening; -6% and -5% for thickening). Captopril improved regional function maintaining positive values for shortening (4% LAD; 3% Cx) and thickening (0.3% LAD; 4% Cx). Similar responses were obtained during partial OP and captopril. Results suggest that captopril produced a significant improvement in the regional function parameters affected by ischemia both in total and partial obstructions.     

Pulmonary edema formation after myocardial infarction and coronary reperfusion: intravascular and extravascular pulmonary fluid volumes. IV

Two studies were performed to assess the importance of coronary reperfusion on pulmonary capillary endothelial permeability in 34 anesthetized dogs. The response of intravascular pulmonary blood volume (PBV) and extravascular lung water (EVLW) was examined using indicator-dilution and postmortem (wet weight/dry weight) techniques. In the first study, six dogs served as sham controls, seven were occluded (LAD) for 45 min, and seven occluded for 45 min and reperfused for 15 min. While PBV was similar in each group, EVLW was greater in the reperfused than nonreperfused dogs (9.5 +/- 0.7 cc/kg vs 8.1 +/- 0.8 cc/kg; P less than .05), and both occluded groups were greater (P less than .01) than the control animals (7.0 +/- 1.0 cc/kg). Similar trends in postmortem wet weight/dry weight data were observed when compared with the in vivo EVLW data. In a second study of 14 open-chest dogs, an LAD ligation was held for 45 min in 14 dogs. In seven dogs, reperfusion was allowed for 15 min. A left atrial (LA) balloon was then inflated in all 14 dogs, increasing left atrial pressure to 25 mmHg in each dog for 90 min. Once again, PBV was similar in both groups, but EVLW was greater at the matched level of LA pressure elevation (14.6 +/- 3.2 cc/kg nonreperfused vs 18.7 +/- 4.1 cc/kg reperfused dogs; P less than .01). Again, postmortem data confirmed these data. Thus, we conclude coronary occlusion accelerates EVLW formation independent of LA pressure. Edema formation is worsened by coronary reperfusion, suggesting that the washout of myocardial toxins from the ischemic myocardium alters endothelial permeability.(ABSTRACT TRUNCATED AT 250 WORDS)     

Exercise training after experimental myocardial infarction increases the ventricular fibrillation threshold before and after the onset of reinfarction in the isolated rat heart

Previous work has shown that exercise training increases the ventricular fibrillation threshold of the isolated perfused rat heart. The aim of our study was to determine whether exercise training that begins after myocardial infarction can similarly increase the ventricular fibrillation threshold. Rats that had suffered an experimental myocardial infarction were subject to a running training program. Thereafter, the ventricular fibrillation threshold was measured before and after the onset of acute reinfarction induced by a second coronary artery ligation. Ventricular fibrillation thresholds were significantly elevated in trained rats during normoxia (13.7 +/- 2.2 vs. 4.7 +/- 0.8 mA, p less than 0.01) and during acute ischemia (6.8 +/- 1.6 vs. 3.0 +/- 0.7 mA, p less than 0.02). The myocardial cyclic AMP level was lower in the nonischemic zone of the trained hearts (0.21 +/- 0.01 vs. 0.28 +/- 0.01 nmol/g, p less than 0.05), which also had lower cyclic AMP levels after epinephrine challenge (0.50 +/- 0.05 vs. 0.73 +/- 0.09 nmol/g, p less than 0.01; 1.41 +/- 0.11 vs. 1.85 +/- 0.09 nmol/g, p less than 0.02 after epinephrine 10(-7) M and 5 x 10(-6) M injection, trained vs. untrained). Both propranolol 10(-6) M and epinephrine 5 x 10(-7) M attenuated the difference in ventricular fibrillation thresholds before and after second coronary artery ligation and eliminated any difference in cyclic AMP content of both the nonischemic and ischemic myocardial tissue.(ABSTRACT TRUNCATED AT 250 WORDS)     

Prediction of immediate ventricular arrhythmias after coronary artery ligation.

OBJECTIVES. Our aim was to test the hypothesis that increased beat to beat morphologic variations in the body surface electrocardiogram (ECG) are associated with fragmented diastolic electrical activity that appears after coronary artery ligation and to correlate the appearance of spontaneous ventricular fibrillation after coronary ligation with the magnitude of the ECG beat to beat variability. BACKGROUND. Unstable and variably delayed electrical activation precedes the development of ventricular fibrillation in dogs with acute ischemia. Detection of these highly variable low amplitude signals from the body surface is currently impossible. We have developed a system designed to measure the degree of beat to beat variability of the ECG. METHODS. With high fidelity electrocardiography, subtle beat to beat ECG morphologic variations were detected in epicardial and body surface electrograms and quantified as the variance of the ECG voltage at specific points of the cardiac cycle. The ratio of the variance at the QRS offset to that of the QRS onset (beat to beat variability index) was then calculated. RESULTS. Ventricular fibrillation developed in 12 of 27 dogs after left anterior descending coronary artery ligation. In 7 of the 12 dogs it occurred immediately (< 15 min) after ligation; in the other 5 it developed late (> 15 min) after ligation. Dogs with subsequently immediate ventricular fibrillation had a significantly higher beat to beat variability index than that of dogs with late or no ventricular fibrillation both before coronary ligation (4.7 +/- 1.4 vs. 1.1 +/- 0.2 and 0.8 +/- 0.1, respectively, p < 0.001) and after ligation (6.4 +/- 2.6, 1.0 +/- 0.6 and 1.2 +/- 0.6, respectively, p < 0.001). In dogs that developed ventricular fibrillation immediately after coronary ligation, the arrhythmia was preceded by fragmented diastolic electrical activity on the epicardial electrogram and a simultaneous increase in the beat to beat morphologic variability of the terminal portion of the body surface ECG QRS complex. CONCLUSIONS. Beat to beat QRS offset morphologic variations appear to be increased before and further increased after coronary artery ligation in dogs that develop ventricular fibrillation immediately after ligation. Increased beat to beat variability index may be associated with the presence of electrophysiologic instability and can predict early ventricular fibrillation.     

Failure of nitroglycerin introduced after prolonged myocardial ischemia to improve collateral blood flow and function in tranquilized dogs

This study investigated whether nitroglycerin can improve ischemic zone blood flow and function when its infusion is delayed following left anterior descending (LAD) occlusion. Nitroglycerin (200 micrograms/min, 11 dogs) or saline (six dogs) was infused for 2 hours starting 2 hours after occlusion. Regional myocardial blood flow (MBF) was measured (9 +/- 1 micron radioactive microspheres) before and at 2 and 4 hours after occlusion. Segmental contraction was determined by cineroentgenography of implanted tantalum markers. For all ischemic samples (defined as MBF less than or equal to 0.4 ml/min/gm), the average improvement in MBF in the epicardial half (EPI) was 0.05 +/- 0.02 ml/min/gm (mean +/- SEM) with nitroglycerin vs 0.06 +/- 0.06 with saline (p greater than 0.5). Improvement in the endocardial half (ENDO) averaged 0.03 +/- 0.03 ml/min/gm with nitroglycerin vs 0.09 +/- 0.08 with saline (p = 0.5). Contraction in the ischemic zone ceased following occlusion and was unaffected by nitroglycerin or saline. Control blood flows in the ischemic region were 22% less in the ENDO (p less than 0.001) and 19% less in the EPI (p less than 0.005) than in nonischemic myocardium. These results indicate that 2 hours after LAD occlusion in dogs, nitroglycerin was unable to improve ischemic zone collateral flow or contractile function compared to untreated controls. Lower ischemic zone control flows indicate that infarct volume expansion may occur within 4 hours after coronary occlusion.     

Role of thromboxane A2 in the cardiovascular response to intracoronary C5a

Intracoronary administration of complement component C5a induces transient decreases in coronary blood flow and regional left ventricular segment shortening, associated with intramyocardial granulocyte trapping. We evaluated the influence of a cyclooxygenase inhibitor (acetylsalicylic acid, n = 8) or a thromboxane A2/prostaglandin H2 receptor antagonist (SQ29548, n = 6) on these C5a-induced cardiovascular responses. Open-chest anesthetized pigs were instrumented to monitor heart rate, arterial blood pressure, left anterior descending coronary blood flow, regional left ventricular segment shortening, and dP/dt. Oxygen content, lactate concentration, leukocyte count, and thromboxane B2, the stable metabolite of thromboxane A2, were measured in arterial and regional coronary venous blood. Repetitive injections of intracoronary C5a (500 ng) given 60 minutes apart showed no tachyphylaxis of the hemodynamic response. However, tachyphylaxis was seen in coronary blood flow changes when injections were spaced 30 minutes apart. An increase in myocardial oxygen extraction and lactate production was observed after intracoronary C5a. Administration of acetylsalicylic acid (50 mg/kg i.v.) attenuated C5a-induced decreases in coronary blood flow (-8 +/- vs. -3 +/- 1 ml/min) and regional left ventricular segmental shortening (-10 +/- 3% vs. -2 +/- 1%) and blocked the maximal increase in coronary venous thromboxane B2 (2.0 +/- 0.1 vs. 0.2 +/- 0.1 pmol/ml plasma). Furthermore, SQ29548 (30 micrograms/kg/min) reduced C5a-induced changes in coronary blood flow (-13 +/- 2 vs. -4 +/- 2 ml/min) and segmental shortening (-14 +/- 2% vs. -3 +/- 1%). Neither cyclooxygenase inhibition nor thromboxane A2/prostaglandin H2 antagonism blocked the decrease in coronary venous granulocyte count.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of intra-aortic balloon counterpulsation on the motion and perfusion of acutely ischemic myocardium. An experimental echocardiographic study.

The effect of intra-aortic balloon counterpulsation (IABC) on the motion and perfusion of ischemic left ventricular posterior myocardium was studied in 30 open-chest dogs, using ultrasound to register motion and 7-10 mu radioactive microspheres to determine perfusion. Circumflex coronary artery ligation produced acute aneurysmal bulging during isovolumetric contraction and diminished ischemic wall velocity during systolic ejection. Myocardial perfusion was determined in five dogs; perfusion of the area supplied by the ligated coronary artery fell from a control value of 72.9 +/- 13.8 (SE) to 30.0 +/- 2.3 cc/100 g/min (P less than 0.05) at 5 minutes after coronary occlusion. IABC was then administered for one hour, with a fall in aortic systolic pressure (112 +/- 6 to 105 +/- 7 mm Hg, P less than 0.05) and rise in peak aortic diastolic pressure (94 +/- 6 to 102 +/- 7 mm Hg, P less than 0.05). Despite this the ischemic area showed no change in perfusion (measured at the same time): 30.0 +/- 2.3 to 28.0 +/- 2.4 cc/100 g/min. Little change in wall motion occurred: aneurysmal bulging decreased modestly (4.5 +/- 0.3 to 3.6 +/- 0.3 mm, P less than 0.05), but ischemic wall velocity did not increase. After cessation of counterpulsation and one hour of coronary reperfusion aneurysmal bulging disappeared and wall velocity improved. The addition of norepinephrine (eight dogs) or nitroprusside (seven dogs) to intraaortic balloon counterpulsation did not cause a significant further improvement in the response of the dyskinesis during the period of ischemia. We conclude that IABC has little effect on ischemic dyskinesis, probably due to its failure to improve perfusion of the acutely ischemic myocardium.     

Effect of acute subendocardial ischemia on ventricular refractory periods

OBJECTIVES: To investigate the impact of acute subendocardial ischemia on the dispersion of ventricular refractory periods. METHODS: Acute subendocardial ischemia was induced in sheep by partial ligation of the left circumflex coronary artery and rapid pacing of the left atrium. The ventricular effective refractory period (ERP) was measured in five areas of the left ventricle by a programmed premature stimulation technique. RESULTS: The average ERP and ERP dispersion remained unchanged in the control group (n=5, P>0.05). In the study group (n=5), the ERP was shortened following subendocardial ischemia. ERP dispersion decreased significantly from 48+/-9 ms to 36+/-13 ms 30 min after the ischemia (P=0.02). There was neither spontaneous nor stimulation-induced ventricular arrhythmia after ischemia. CONCLUSION: Acute subendocardial ischemia leads to a homogenous reduction of ventricular ERP. This may partially explain why subendocardial ischemia is associated with a low incidence of ventricular arrhythmia.     

Inhomogeneity of ventricular refractory period in canine heart with quinidine-induced long QT interval: a comparative study on effects of heart rate, isoprenaline, and lignocaine

In anaesthetised open chest dogs, 30 mg . kg-1 of quinidine sulphate was injected intravenously over 5 min to produce QT prolongation. The sinus node was crushed. Effective refractory period (ERP) was determined at eight test points of the right ventricle using extra-stimuli after every seven basic ventricular pacings. Stimuli were of 2 ms duration and 1.5 times diastolic threshold. Temporal dispersion was estimated as the difference between the maximum and the minimum ERP of eight test points. Cycle lengths of basic ventricular drive were 700, 600, 500, and 400 ms. Time course of changes in ERP and its temporal dispersion was tested in five dogs. The effect of a 2 mg . kg-1 bolus injection followed by 70 micrograms . kg-1 . min-1 drip infusion lignocaine, on quinidine-induced changes in ERP was studied in eight dogs, and that of a 0.06 microgram . kg-1 . min-1 infusion of isoprenaline, was tested in six dogs. ERP was significantly prolonged after quinidine injection (220 +/- 20 vs 258 +/- 25 ms n = 19, basic cycle length = 500 ms, p less than 0.001). Temporal dispersion was also increased after quinidine (18 +/- 9 vs 33 +/- 12 ms n = 19, basic cycle length = 500 ms, p less than 0.001). With shortening of basic cycle length (BCL), ERPs were shortened significantly. Temporal dispersion, however, did not change. Lignocaine prolonged ERP even further (250 +/- 25 vs 273 +/- 16 ms BCL = 500 ms, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

神经节丛消融对心室不应期和室性心律失常发生的影响

目的 研究心脏神经节丛(GP)消融对心室不应期和室性心律失常发生的影响.方法 24只杂种犬随机分为GP消融组(n=12)和对照组(n=12).在左、右心室表面分别缝一10极冠状静脉窦电极导管记录心底部至心尖部4个不同部位电图,分别测量各个部位GP消融前和消融后伴或不伴迷走神经刺激时的有效不应期(ERP),测量ERP的空...     

Electrophysiologic substrate associated with pacing-induced heart failure in dogs: potential value of programmed stimulation in predicting sudden death.

To investigate the possible mechanisms of sudden death and the potential role of electrophysiologic testing in congestive heart failure, this study evaluated the electrophysiologic substrate in a model of heart failure induced by rapid pacing. Seventeen mongrel dogs underwent cardiac pacing at 220 to 240 beats/min for 5 weeks (paced group) and 11 other dogs served as a sham-operated control group. Rapid pacing of the right ventricle produced clinical and hemodynamic features of congestive heart failure. Dogs in the paced group had prolonged cardiac conduction time as reflected by longer epicardial activation time (36.1 +/- 2.4 vs. 30.8 +/- 0.8 ms, p less than 0.05). The ventricular effective refractory period was significantly prolonged after the development of heart failure (141 +/- 4 vs. 177 +/- 5 ms, p less than 0.01, at a basic pacing cycle length of 300 ms), whereas no significant change was found in the control group (140 +/- 4 vs. 145 +/- 4 ms, p = NS). The prolongation of the ventricular effective refractory period correlated with an increase in left ventricular end-diastolic pressure (r = 0.55, p less than 0.001) and the ventricular effective refractory period correlated inversely with cardiac index (r = -0.49, p less than 0.025). The rest membrane potential of ventricular muscle was less negative in the paced group compared with the control group (-80.7 +/- 2.2 vs. -85.6 +/- 2.2 mV, p less than 0.05). Intracellularly recorded action potential duration of ventricular muscle was longer in the paced than in the control group (236 +/- 9.8 vs. 198.9 +/- 2.6 ms, p less than 0.01), action potential duration at 90% repolarization).(ABSTRACT TRUNCATED AT 250 WORDS)     

Protection against autonomic denervation following acute myocardial infarction by preconditioning ischemia

To examine the effects of ischemic preconditioning on efferent autonomic responses following acute transmural myocardial ischemia/infarction (MI), the time course and extent of efferent sympathetic and vagal denervation were compared between control dogs that received a one-stage sustained coronary occlusion and preconditioned dogs that received four 5-minute coronary occlusions separated by 5 minutes of reperfusion before sustained occlusion. Effective refractory periods (ERP) basal and apical to MI were determined in the baseline state and during neural stimulation before and after preconditioning occlusions and 20, 60, 120, and 180 minutes after sustained occlusion by ligature ligation of diagonal branches of the left anterior descending coronary artery. In 10 control dogs with transmural MI, ERP shortening induced by bilateral ansae subclaviae stimulation (4-msec pulses, 2-4 Hz and 2-4 mA) was unchanged at basal sites but was attenuated at apical sites. Four of 40 apical test sites exhibited efferent sympathetic denervation (less than or equal to 2 msec shortening) 20 minutes after sustained occlusion. Thirteen of 40 apical sites became denervated during a 3-hour period. In 10 preconditioned dogs, ERP shortening at apical sites was unchanged after preconditioning occlusions and during the first 60 minutes of sustained ischemia but was attenuated at 120 minutes. Three of 40 apical test sites became denervated during a 3-hour period. The cumulative percentage of denervated apical test sites was significantly less in the preconditioned group compared with the control group (p = 0.006) despite a comparable degree of subepicardial involvement in the MI (8.2 +/- 1.0% vs. 8.4 +/- 1.4%, the ratio to the left ventricular circumference, mean +/- SEM). In 11 control dogs tested for efferent vagal response after MI, ERP prolongation induced by bilateral vagal stimulation (4-msec pulses, 20 Hz with current strength 0.05 mA greater than that required to produce asystole) was unchanged at basal sites, but was attenuated at apical sites, and five of 44 test sites exhibited denervation (less than or equal to 1 msec prolongation) 20 minutes after sustained coronary occlusion. Fourteen of 40 apical sites became denervated during a 3-hour period. In 10 preconditioned dogs, vagally induced ERP prolongation was unchanged both at basal and apical sites, and none of 36 apical test sites exhibited denervation after preconditioning and during a 3-hour period of sustained coronary occlusion (p less than 0.001 vs. control group) despite a comparable degree of subendocardial involvement in the MI (11.8 +/- 0.8% vs. 11.9 +/- 1.3%).(ABSTRACT TRUNCATED AT 400 WORDS)