Experimental Acute Myocardial Ischemia Research Articles

QUANTIFICATION OF CARDIAC KINETIC ENERGY AND ITS CHANGES DURING TRANSMURAL MYOCARDIAL INFARCTION ASSESSED BY MULTI-DIMENSIONAL SEISMOCARDIOGRAPHY

Objective: Seismocardiography (SCG) records cardiac and blood-induced motion transmitted to the chest surface as vibratory phenomena. Evidences demonstrate that acute myocardial ischemia (AMI) profoundly affects the SCG signals. Multidimensional SCG records cardiac vibrations in linear and rotational dimensions and scalar parameter of kinetic energies can be computed. We speculate that AMI and revascularization profoundly modify cardiac kinetic energy as recorded by SCG. Design and method: Under general anesthesia, 21 swines underwent 90 minutes myocardial ischemia induced by percutaneous subocclusion of proximal left anterior descending (LAD) coronary artery and subsequent revascularization. Invasive hemodynamic parameters were continuously recorded. SCG was recorded during the baseline (BSL); immediately and 80 min after LAD subocclusion (AMI t0; AMIt80, respectively); immediately and 60 min after LAD reperfusion (RE t0, RE t80, respectively). iK was automatically computed for each cardiac cycle (iK_CC) in linear (iK_Lin) and rotational (iK_Rot) dimensions. iK was calculated during systole and diastole (iK_Sys and (iK_Dia, respectively). Results: Compared to baseline, troponins increased from 13.0 [6.5; 21.3] ng/dL to 170.5 [102.5; 475.0] ng/dL and LVEF dropped from 65.0 ± 0.0% to 30.6 ± 5.7% at the end of revascularization (both p < 0.0001). In the linear dimension, iK_Lin-CC, iK_Lin-Sys, iK_Lin-Dia dropped by 43%, 52%, 53% respectively (p < 0.0001, p < 0.0001, p = 0.03, respectively) from baseline to the end of reperfusion. In the rotational dimension, iK_Rot-CC and iK_Rot-Sys dropped by 30% and 36% respectively (p = 0.0006, p < 0.0001), but iK_Rot-Dia did not change (p = 0.41). The figure below represents the evolution of waveforms of iK computed from the SCG signals during the experimental procedure, specifically during BSL, AMIt0, AMIt80, REt0, REt60. Linear (B) and rotational (C) iK drop at AMIt0 compared to BSL, remain below baseline values during the all duration of AMI and returns to normal level during reperfusion. The hemodynamic parameters, except the pulmonary artery pulse pressure, were significantly correlated with parameters of iK. Conclusions: Multidimensional SCG can detect changes in myocardial contractility during experimental AMI, providing information on the cardiac contractile status expressed in term of iK. This automatic system may empower health care providers and patients to remotely monitor cardiovascular status in the near future.

Quantification of Cardiac Kinetic Energy and Its Changes During Transmural Myocardial Infarction Assessed by Multi-Dimensional Seismocardiography.

Introduction: Seismocardiography (SCG) records cardiac and blood-induced motions transmitted to the chest surface as vibratory phenomena. Evidences demonstrate that acute myocardial ischemia (AMI) profoundly affects the SCG signals. Multidimensional SCG records cardiac vibrations in linear and rotational dimensions, and scalar parameters of kinetic energy can be computed. We speculate that AMI and revascularization profoundly modify cardiac kinetic energy as recorded by SCG.Methods: Under general anesthesia, 21 swine underwent 90 min of myocardial ischemia induced by percutaneous sub-occlusion of the proximal left anterior descending (LAD) coronary artery and subsequent revascularization. Invasive hemodynamic parameters were continuously recorded. SCG was recorded during baseline, immediately and 80 min after LAD sub-occlusion, and immediately and 60 min after LAD reperfusion. iK was automatically computed for each cardiac cycle (iKCC) in linear (iKLin) and rotational (iKRot) dimensions. iK was calculated as well during systole and diastole (iKSys and iKDia, respectively). Echocardiography was performed at baseline and after revascularization, and the left ventricle ejection fraction (LVEF) along with regional left ventricle (LV) wall abnormalities were evaluated.Results: Upon LAD sub-occlusion, 77% of STEMI and 24% of NSTEMI were observed. Compared to baseline, troponins increased from 13.0 (6.5; 21.3) ng/dl to 170.5 (102.5; 475.0) ng/dl, and LVEF dropped from 65.0 ± 0.0 to 30.6 ± 5.7% at the end of revascularization (both p < 0.0001). Regional LV wall abnormalities were observed as follows: anterior MI, 17.6% (three out of 17); septal MI, 5.8% (one out of 17); antero-septal MI, 47.1% (eight out of 17); and infero-septal MI, 29.4% (five out of 17). In the linear dimension, , , and dropped by 43, 52, and 53%, respectively (p < 0.0001, p < 0.0001, and p = 0.03, respectively) from baseline to the end of reperfusion. In the rotational dimension, and dropped by 30 and 36%, respectively (p = 0.0006 and p < 0.0001, respectively), but did not change (p = 0.41). All the hemodynamic parameters, except the pulmonary artery pulse pressure, were significantly correlated with the parameters of iK, except for the diastolic component.Conclusions: In this very context of experimental AMI with acute LV regional dysfunction and no concomitant AMI-related heart valve disease, linear and rotational iK parameters, in particular, systolic ones, provide reliable information on LV contractile dysfunction and its effects on the downstream circulation. Multidimensional SCG may provide information on the cardiac contractile status expressed in terms of iK during AMI and reperfusion. This automatic system may empower health care providers and patients to remotely monitor cardiovascular status in the near future.

Hemodynamics in experimental acute myocardial ischemia against the background of the use of substance PK-66 in comparison with the cordarone

The aim of the study was to study the effect of PK-66 substances on hemodynamic parameters under experimental acute myocardial ischemia compared with cordarone.Materials and methods. The experiments were carried out on 21 rabbits of the chinchilla breed. Acute myocardial ischemia (AMI) was modeled by intravenous injection of epinephrine at a dose of 0.2 mg / kg and caffeine sodium benzoate at a dose of 25 mg / kg. In the studies carried out, the Cordarone compounds and the PC-66 test sample were used. The maximum pressure in the left ventricle (MPLV), mean arterial pressure (MAP), total peripheral vascular resistance (TPVR), and minute volume (MV) were recorded. The initial values of the parameters studied were recorded immediately after the administration and after 30 minutes. after administration of the test substance, immediately after the introduction of the analyzers, and also after 15 and 30 minutes. after modeling pathology.Results Simulation of AMI in rabbits, accompanied by a decrease in MV, caused by a decrease in contractile activity of the myocardium, also showed a simultaneous decrease MPLV in and a significant increase in TPVR, which is caused by a sudden decrease in MV and a decrease in MAP. The introduction of cordarone reduces the changes observed in the modeling of pathology (6.33–10.36 %). The use of PK-66 neutralizes changes in maximum pressure in the left ventricle observed immediately after modeling AMI, followed by a decrease in this parameter after 15 minutes. and normalization after 30 minutes. The prophylactic administration of the PK-66 test sample did not significantly influence the modeling of AMI. Substance PK-66 and cordarone showed a close unidirectional effect in AMI, reducing the changes in SAT, MPLV, MAP, and TPVR in pathology.Conclusions. Acute ischemia of the myocardium in rabbits is characterized by an increase: total peripheral resistance of blood vessels, a decrease in the minute volume of blood and systolic blood pressure. Prophylactic administration of PK-66 leads to normalization of indicators of general hemodynamics in AMI, not inferior in effectiveness to the drug comparison kordaronu.

Pharmacodynamics of &lt;I&gt;Danshen&lt;/I&gt; co-microemulsion in treatment of experimental acute myocardial ischemia induced by pituitrin in rats

Pharmacodynamics of &lt;I&gt;Danshen&lt;/I&gt; co-microemulsion in treatment of experimental acute myocardial ischemia induced by pituitrin in rats

Effect of essential oil of Syringa pinnatifolia Hemsl. var. alashanensis on ischemia of myocardium, hypoxia and platelet aggregation

Aim of the study To investigate the cardioprotective potential of Syringa pinnatifolia Hems1. var. alashanensis essential oil (SPEO) against experimental acute myocardial ischemia (AMI), hydrogen peroxide (H 2O 2)-induced myocyte injury and activities against hypoxia and platelet aggregation. Materials and methods Wistar rats, Kunming mice and primary cultured rat neonatal myocytes were used in this study. AMI in rats was induced by ligation of the left anterior descending (LAD) coronary artery, and deviation of ST-segment, as well as changes of myocardial enzyme activities were observed. Hypoxia test in Kunming mice was performed to evaluate the effect of SPEO against hypoxia. The protective effect of SPEO on H 2O 2-induced cell injury was evaluated in terms of cell viability assay. The in vitro effect of SPEO against platelet aggregation was studied using adenosine 5′-diphosphate (ADP) as agonist. Results Administration of SPEO reduced deviation of ST-segment, decreased the levels of lactate dehydrogenase (LDH), creatine kinase (CK) and Troponin T (TnT) while increased the activities of superoxide dismutase (SOD). The protective role of SPEO was further confirmed by histopathological examination. In the hypoxia test, both 8 and 32 mg/kg of SPEO could prolong survival time of mice under hypoxia condition. At the meantime SPEO showed remarkable protective effect on cultured rat myocyte death induced by H 2O 2. SPEO also inhibited ADP-induced rat platelet aggregation by 47.4%, 37.0% and 32.9% at the dose of 5, 2.5 and 1.25 μg/mL, respectively. Conclusions These results suggest that SPEO possessing activities against hypoxia, oxidative stress and platelet aggregation has a significant protective effect against experimental myocardial ischemia.

Effect of Yuxintong"Equation missing" capsule on serum creatine phosphokinase activity and plasma endothelin concentration in acute myocardial ischemic dogs) capsule on serum creatine phosphokinase activity and plasma endothelin concentration in acute myocardial ischemic dogs

The protective effect of the traditional Chinese compound medicine Yuxingtong (YXT) in capsule form on the experimental acute myocardial ischemia formation has been studied in dogs. The plasma endothelin concentration and serum creatine phosphokinase activity were measured after coronary occlusion in different medication groups and compared with the saline control group. Results showed that YXT could significantly lowered the plasma endothelin concentration and the serum creatine phosphokinase activity, it suggested that both YXT and diltiazem have the similar protective effect on acute myocardial ischemia and necrosis in dogs.

804-3 A Double Blind Randomized Trial of a 24 Hour Infusion of Magnesium Sulphate in Unstable Angina

Magnesium (Mg2+) has been shown to reduce coronary spasm, have favorable hemodymamic effects, inhibit platelet function, reduce arrhythmias, modulate autonomic function, reduce catecholamine secretion and to be protective during experimental acute myocardial ischemia. Sixty-two consecutive patients with unstable angina (rest pain &lt; 24 hours, ST/T changes and normal admission CK) were randomized in a double-blind fashion to Mg2+ (8 mmol bolus, then 3.0 mmol/h for 24 hours) or placebo within 12 hours of admission. All patients received aspirin, β blockade, iv nitrates and heparin, provided no contraindications existed. Four consecutive 12 hour urine collections were started at study entry for estimation of catecholamines (n = 31) or β thromboglobulin (n = 31). 84% underwent predischarge angiography. Baseline characteristics and extent of coronary disease were similar in both groups. Serum Mg2+ rose from 0.91 ± 0.02 to 1.71 ± 0.05 mmol/l (mean ± SEM) in the Mg2+ group. CKMB release was less in the Mg2+ group at 6 and 24 hours (28.3 ± 7.4 vs 6.6 ± 1.2 ng/ml at 6 hrs, p &lt; 0.05). Regression of T wave changes on the 24 hour ECGs (compared with admission ECGs) occurred more frequently in the Mg2+ group (11 patients vs 0 patients, p &lt; 0.005). On 48 hour Holter monitoring, a similar proportion had transient myocardial ischemia (TMI) in the two groups (16 (52%) in the Mg2+ group vs 15 (48%) in the placebo group), however there were fewer episodes of TMI in the Mg2+ group (57 vs 118, p &lt; 0.0001) with a median total duration of 31.45 vs 102.73 mins respectively (p = ns). Frequency of ventricular ectopy and non-sustained ventricular tachycardia were similar in both groups. Heart rate variability was significantly lower in the placebo group in the 24 hours following, but not during, the infusion. Epinephrine excretion was lower in the Mg2+ group in the first 12 hour sample (1.05 ± 0.20 vs 1.61 ± 0.41 ng/mmol creat., p &lt; 0.051, with no significant difference in norepinephrine excretion. Urinary β thromboglobulin was similar in both groups in all collections. Thus Mg2+ appears to reduce CKMB release, ECG progression and catecholamines in the acute phase of unstable angina with no effect on β thromboglobulin excretion suggesting that its effect may be mediated via autonomic modulation but not platelet function. A larger scale trial investigating the effect of Mg2+ on mortality is warranted.

Fibronectin Penetration into Heart Myocytes Subjected to Experimental Ischemia by Coronary Artery Ligation

Using confocal microscopy and immunocytochemistry we have studied early changes in distribution of fibronectin (FN) in myocardial cells of rats subjected to experimental acute myocardial ischemia (AMI) by coronary ligation for several periods of 0.5 h to 6 days. In sham-operated and nonoperated rats, FN was present in the interstitium around the myocytes, and in their transverse tubules (TT). Already after 0.5 h of ischemia there was a well-defined increase of immunoreactive FN in focal areas of the interstitium of the hypoperfused portion, and distinct penetration into adjacent myocytes. The early penetration of FN into myocytes appears to follow a path through the TT, with a codistribution with actin in the I bands. This process precedes a total and diffuse infiltration of FN into the cytoplasm of disintegrating myocytes at later stages of coronary occlusion.

Serial production of controlled periods of temporary heart block used to unmask and assess latent ventricular automaticity during experimental acute myocardial ischemia

This study examined the onset, time course of development and response to overdrive stimulation of ventricular tachycardia in 10 dogs that underwent a Harris two-stage ligation of the left anterior descending coronary artery. Transient (12 +/- 3 minutes) complete atrioventricular (AV) block was produced 2, 3, 4, 5, 8, 12, 16, 20 and 24 hours after onset of infarction through selective injection of physostigmine salicylate into the AV node artery. Seven of the 10 dogs had early transient arrhythmic episodes that occurred within 20 to 40 minutes after coronary occlusion but none of the dogs had any spontaneous ventricular tachycardia in the ensuing 2 hours. Two hours after left anterior descending coronary artery ligation, complete AV block unmasked in every dog a slow (37 +/- 9 beats/min) AV junctional rhythm readily suppressed by overdrive. Three hours after coronary ligation, AV block revealed a monomorphic ventricular tachycardia (106 +/- 10 beats/min) in 3 of the 10 dogs. Four and five hours after coronary ligation, five and eight dogs, respectively, had ventricular tachycardia during AV block and in three the tachycardia was polymorphic. The two remaining dogs did not develop ventricular tachycardia during the 24 hours of observation. Ventricular tachycardia always began abruptly, first with brief and then longer bursts. Soon after onset the rate of tachycardia began to increase to reach a plateau 2 to 3 hours later at frequencies 21 +/- 9% greater than the initial tachycardia rate. Concomitant with this increase in rate there was a steady decline of overdrive suppressibility and during the plateau phase there was little or no overdrive suppression.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of parathyroid extract on the course of experimental acute myocardial ischemia in rats

Effect of parathyroid extract on the course of experimental acute myocardial ischemia in rats

Increased R-wave amplitude induced by acute myocardial ischemia in the dog: A predictor of malignant ventricular arrhythmias

The ability of an increase of 25 % or greater in the sum of R-wave amplitudes in leads X, Y, Z, L 2, and V 5 to predict the occurrence of malignant ventricular arrhythmias (10 or more ventricular premature beats/min, ventricular tachycardia [5 or more consecutive premature beats], and/or fibrillation) was evaluated in 17 dogs during experimental acute myocardial ischemia. Each dog underwent a 15 minute ligation of the left anterior descending coronary artery followed by reperfusion and after recovery, 2 hours later, a 15 minute ligation of the circumflex coronary artery. During ligation of the left anterior descending coronary artery, 12 of 17 dogs (71%) showed no R-wave increase and no arrhythmias (true-negative response). In 5 (29%) of 17 dogs malignant ventricular arrhythmias developed: 2 of 5 (40%) dogs with arrhythmias had a concomitant R-wave increase (true-positive response), and 3 of 5 (60%) with arrhythmias had a less than 25% increase in R-wave amplitude (false-negative results). During circumflex coronary artery ligation, 13 of 17 (76%) dogs showed both R-wave increases and arrhythmias (true-positive response). Four (24%) of 17 dogs had no arrhythmias: 3 of 4 (75%) with no arrhythmias also had a less than 25% increase in R-wave amplitude (true-negative response), whereas 1 of 4 (25%) dogs with no arrhythmias had an increase in R-wave amplitude (false-positive response). In dogs with both arrhythmias and R-wave increases, R-wave changes preceded the onset of arrhythmias by a mean (± standard deviation) of 1 minute 27 seconds (± 43 seconds). Overall, R-wave increases were highly sensitive (83%), specific (94%), and predictive (94%) for the occurrence of malignant ventricular arrhythmias during experimental acute myocardial ischemia.

Influence of dobutamine on regional myocardial blood flow and ventricular performance during acute and chronic myocardial ischemia in dogs.

The data from this study document that dobutamine is a powerful inotropic agent in anesthetized dogs with acute myocardial ischemia and in awake, unsedated ones with chronic myocardial infarction. Dobutamine significantly increases heart rate at relatively small doses in anesthetized dogs with acute myocardial ischemia but considerably larger amounts of dobutamine are required to significantly increase heart rate in awake, unsedated dogs with myocardial infarction. Dobutamine also significantly increases regional myocardial blood flow to all areas of the heart at 20mug/kg/min in both anesthetized dogs with acute myocardial ischemia and awake, unsedated ones with myocardial infarction. However, in anesthetized dogs 20mug/kg/min of dobutamine significantly increases epicardial ST-segment elevation during acute myocardial ischemia. Propranolol prevents the inotropic and chronotropic effects of dobutamine in both anesthetized and awake, unsedated dogs. This study suggests that during experimental acute myocardial ischemia dobutamine given at doses that significantly increase heart rate and contractility may increase the extent of myocardial damage. The data also suggest that this agent should be of value in the setting of severe myocardial depression without associated severe coronary artery disease to increase cardiac contractility at doses that do not markedly alter heart rate. The hemodynamic and coronary blood flow effects of dobutamine in patients with and without severe coronary artery disease should be evaluated.

Electrode catheter recordings during malignant ventricular arrhythmias following experimental acute myocardial ischemia. Evidence for re-entry due to conduction delay and block in ischemic myocardium

Electrode catheter recordings during malignant ventricular arrhythmias following experimental acute myocardial ischemia. Evidence for re-entry due to conduction delay and block in ischemic myocardium

Beneficial Effects of Vagal Stimulation and Bradycardia During Experimental Acute Myocardial Ischemia

It is commonly believed that vagally-mediated bradycardia predisposes to ventricular fibrillation (VF) during acute myocardial ischemia. Recent experimental studies, however, have shown that bradycardia and vagal stimulation independently raise the threshold for electrically induced VF in the ischemic canine heart. To determine the influence of vagal stimulation on the spontaneous development of VF occurring during acute myocardial ischemia, open-chest dogs with acute coronary occlusion were observed with and without electrical vagal stimulation. When heart rate was allowed to fall, mean time to VF was 14.7 ± 2.1 min ( se ) in the control dogs (heart rate about 180/min), 23.4 ± 1.9 ( P &lt; 0.01) in the dogs with low intensity vagal stimulation (heart rate about 100/min), and 28.6 ± 0.9 ( P &lt; 0.001) in dogs with high intensity vagal stimulation (heart rate about 60/min). Only 10% of the control animals survived after 30 min of occlusion compared with 40% (NS) of the dogs with low intensity vagal stimulation and 71% ( P &lt; 0.05) of the dogs with high intensity vagal stimulation. Thus, vagal stimulation and bradycardia were associated with a postponement or prevention of VF. In a second series of animals with heart rate maintained constant by right ventricular pacing, vagal stimulation continued to exert a protective effect against the development of VF. Time to VF was increased from 11.0 ± 2.0 min in control animals to 22.6 ± 2.5 in dogs with vagal stimulation ( P &lt; 0.005), and percent survival was enhanced (12% in control animals versus 57% in the vagally stimulated group, P &lt; 0.02). Similar results were observed in a third series of dogs in which electrical stimulation was applied to the peripheral ends of the cut cervical vagi. We conclude that vagal stimulation, with or without accompanying bradycardia, reduces the incidence of spontaneous VF in experimental coronary occlusion. Thus, enhanced vagal tone might act to reduce, rather than increase, the risk of arrhythmic death occurring during acute myocardial ischemia in man.

Beneficial electrophysiologic effects of nitroglycerin during acute myocardial infarction

Nitroglycerin reduces ischemic injury after experimental coronary occlusion. To determine whether it also has the potential of protecting the heart against the development of serious ventricular arrhythmias, the effects of nitroglycerin on electrical stability of acutely ischemic myocardium were determined in open chest dogs. Electrical stability of the ventricle was assessed by measuring ventricular fibrillation threshold before and after acute myocardial ischemia was produced by occlusion of the left anterior descending coronary artery. Ventricular fibrillation threshold was measured in a random manner under conditions of nonischemia, ischemia, ischemia plus nitroglycerin, and simultaneous infusion of phenylephrine to maintain mean systemic arterial pressure at control levels. Heart rate was kept constant at 120 beats/min by destruction of the atrioventricular node and use of ventricular pacing. In the absence of ischemia ventricular fibrillation threshold was 77 ± 5 milliamperes (ma), a value unaffected by either nitroglycerin or phenylephrine. After 6 minutes of acute myocardial ischemia, ventricular fibrillation threshold was reduced to 30 ± 6 ma ( P <0.01). When nitroglycerin was infused at a rate of 200 μg/min (with a reduction in arterial pressure of 24 percent), ventricular fibrillation threshold after 6 minutes of acute ischemia increased from 30 ± 6 to 55 ± 3 ma ( P < 0.005). Restoration of arterial pressure by phenylephrine during infusion of nitroglycerin further raised the ventricular fibrillation threshold to 75 ± 6 ma, a value identical to that present in nonischemia. Thus, nitroglycerin enhances electrical stability of the heart during experimental acute myocardial ischemia, an effect probably related to reduction of ischemic injury. Since the ventricular fibrillation threshold increases even further after arterial pressure is restored to control levels, this beneficial electrophysiologic effect is probably caused by some action of nitroglycerin other than reduction in myocardial oxygen consumption mediated by decreased afterload.

Electrical stability of acutely ischemic myocardium. Influences of heart rate and vagal stimulation.

Previous investigations have shown that a slower heart rate (HR) and myocardial ischemia independently diminish the electrical stability of the heart. It therefore was suggested that increasing heart rate during myocardial infarction might diminish the incidence of serious ventricular arrhythmias. However, since increased HR during experimental acute myocardial ischemia augments the degree of ischemia, an evaluation of the presumed "protective" effects of increased HR on the electrical stability of acutely ischemic myocardium was undertaken. The differences in refractory periods (RP) of eight contiguous areas of the left ventricle were determined as a function of HR. In nonischemic myocardium, the disparity of RP was less at an HR of 180 than 60. However, in ischemic myocardium the disparity increased in three of six animals as the HR was increased from 60 to 90, in seven of 10 animals as HR was increased from 60 to 120, and in all animals when the HR was increased from 60 to 180. The increased disparity of RP is believed to favor development of reentrant arrhythmia. The vulnerability of the heart to develop ventricular fibrillation was assessed by determining ventricular fibrillation threshold (VFT). During ischemia, VFT was not only an inverse function of HR but also was found to be independently influenced by electrical stimulation of the cervical vagus nerves. In the absence of vagal stimulation VFT was lowered in only one of four dogs as HR was increased from 50 to 90, but decreased 30% ( P &lt; 0.01) as HR reached 120 and 74% at 180 beats/min. When vagal stimulation was used to control HR VFT was lowered 37% as HR was increased from 50 to 60 to 90 ( P &lt; 0.05). We conclude that increasing HR within a physiologic range by diminishing vagal tone during myocardial ischemia decreases electrical stability of the ventricle by (1) increasing ischemia consequent to the rate-induced increase in myocardial oxygen requirements, and (2) a direct electrophysiologic action of the vagus on the ventricular myocardium.

Coronary artery occlusion in the conscious dog. Effects of alterations in heart rate and arterial pressure on the degree of myocardial ischemia.

Bradycardia, with or without hypotension, frequently occurs in the early phases of acute myocardial infarction. To determine the relative effects of alterations in heart rate and blood pressure on the degree of ischemic injury, the left anterior descending coronary artery was occluded for 15-min periods in closed-chest conscious dogs by inflating a balloon cuff previously implanted around the artery. The degree of myocardial ischemia was estimated by summating the S-T elevation recorded from 12 myocardial electrodes. Heart rate was increased by atropine or pacing and decreased by electrical stimulation of the vagus nerve. Hypotension was produced by venesection (average decrease in mean BP, 56 mm Hg). At normal arterial pressures there was a positive correlation between percent change in heart rate (range 30-215 beats/min) and percent change in S-T elevation (y = 0.75 X + 30.2, r = 0.93, P &lt; 0.01). When myocardial ischemia was induced during hypotension and bradycardia, S-T elevation totaled 68 mv at 15 min of ischemia. When heart rate was increased to control levels in the presence of hypotension S-T elevation during myocardial ischemia was greater (mean difference 29 mv, P &lt; 0.05). In contrast, when blood pressure was increased to control in the presence of bradycardia, S-T elevation in seven of 10 dogs was less than during hypotension and bradycardia. Thus, during experimental acute myocardial ischemia, hypotension induced by hemorrhage increases ischemic injury, and bradycardia reduces it. It is concluded that in acute myocardial ischemia increases in heart rate, even from slow baseline rates; may be deleterious to the myocardium. It remains to be determined whether alterations in the degree of myocardial ischemia induced by hemorrhagic-hypotension are analogous to those caused by the type of hypotension that often accompanies bradycardia occurring during acute myocardial infarction in man.

Relative effectiveness of three antiarrhythmic agents in the treatment of ventricular arrhythmias in experimental acute myocardial ischemia

Since ventricular arrhythmias complicating acute myocardial infarction in man have an uncetain course, an animal model of acute ischemia was used to compare three commonly used agents—procainamide, lidocaine, and diphenylhydantoin. A total of 150 dogs were divided into “treatment only” and “prophylaxis plus treatment” groups for each of the three agents. Twenty additional dogs served as untreated controls. The arterial branch (left circumflex or anterior descending branch) had no effect on ultimate success in preventing ventricular fibrillation with drug therapy for at least 4 hours. Ninety per cent of untreated controls developed fatal ventricular fibrillation within 4 hours. Among the “treatment only” groups 4 hour survival with procainamide (80 per cent) was significantly higher than with lidocaine (45 per cent) or diphenylhydantoin (56 per cent). Prophylactic administration of drugs following S-T-segment elevation but preceding ventricular arrhythmias did not increase survival rate. Following acute myocardial ischemia in the previously undamaged heart, procainamide appears to afford greater protection against ventricular fibrillation than the other two agents.

Acute effects of increased serum osmolality on left ventricular performance.

Acute effects of increased serum osmolality on left ventricular performance.

A technique for ventricular pacing from the His bundle of the intact heart.

A technique for ventricular pacing from the His bundle of the intact heart.