alpha-Methylnorepinephrine, a selective alpha2-adrenergic agonist for cardiac resuscitation.

OBJECTIVES: The purpose of this study was to investigate the effects of a selective alpha2-adrenergic agonist, alpha-methylnorepinephrine (alphaMNE) as an alternative vasopressor agent during cardiopulmonary resuscitation (CPR). BACKGROUND: For more than 40 years, epinephrine has been the vasopressor agent of choice for CPR. Its beta- and alpha1-adrenergic effects increase myocardial oxygen consumption, magnify global myocardial ischemia and increase the severity of postresuscitation myocardial dysfunction. METHODS: Ventricular fibrillation (VF) was induced in 20 Sprague-Dawley rats. After 8 min of untreated VF, mechanical ventilation and precordial compression began. AlphaMNE, epinephrine or saline placebo was injected into the right atrium 2 min after the start of precordial compression. As an additional control, one group of animals was pretreated with alpha2-receptor blocker, yohimbine, before injection of alphaMNE. Defibrillation was attempted 4 min later. Left ventricular pressure, dP/dt40, negative dP/dt and cardiac index were measured for an interval of 240 min after resuscitation. RESULTS: Except for saline placebo and yohimbine-treated animals, comparable increases in coronary perfusion pressure were observed after each drug intervention. All animals were successfully resuscitated. Left ventricular diastolic pressure, cardiac index, dP/dt40 and negative dP/dt were more optimal after alphaMNE; this was associated with significantly better postresuscitation survival. Pretreatment with vohimbine abolished the beneficial effects of alphaMNE. CONCLUSIONS: The selective alpha2-adrenergic agonist, alphaMNE, was as effective as epinephrine for initial cardiac resuscitation but provided strikingly better postresuscitation myocardial function and survival.     

The effects of biphasic and conventional monophasic defibrillation on postresuscitation myocardial function.

OBJECTIVES: The purpose of this study was to compare the effects of biphasic defibrillation waveforms and conventional monophasic defibrillation waveforms on the success of initial defibrillation, postresuscitation myocardial function and duration of survival after prolonged ventricular fibrillation (VF). BACKGROUND: We have recently demonstrated that the severity of postresuscitation myocardial dysfunction was closely related to the magnitude of the electrical energy of the delivered defibrillation shock. In the present study, the effects of fixed 150-J low-energy biphasic waveform shocks were compared with conventional monophasic waveform shocks after prolonged VF. METHODS: Twenty anesthetized, mechanically ventilated domestic pigs were investigated. VF was induced with an AC current delivered to the right ventricular endocardium. After either 4 or 7 min of untreated ventricular fibrillation (VF), the animals were randomized for attempted defibrillation with up to three 150-J biphasic waveform shocks or conventional sequence of 200-, 300- or 360-J monophasic waveform shocks. If VF was not reversed, a 1-min interval of precordial compression preceded a second sequence of up to three shocks. The protocol was repeated until spontaneous circulation was restored or for a total of 15 min. RESULTS: Monophasic waveform defibrillation after 4 or 7 min of untreated VF resuscitated eight of 10 pigs. All 10 pigs treated with biphasic waveform defibrillation were successfully resuscitated. Transesophageal echo-Doppler, arterial pressure and heart rate measurements demonstrated significantly less impairment of cardiovascular function after biphasic defibrillation. CONCLUSIONS: Lower-energy biphasic waveform shocks were as effective as conventional higher energy monophasic waveform shocks for restoration of spontaneous circulation after 4 and 7 min of untreated VF. Significantly better postresuscitation myocardial function was observed after biphasic waveform defibrillation.     

A comparison of biphasic and monophasic waveform defibrillation after prolonged ventricular fibrillation

STUDY OBJECTIVE: To compare the effects of biphasic defibrillation waveforms and conventional monophasic defibrillation waveforms on the success of initial defibrillation, postresuscitation myocardial function, and duration of survival after prolonged duration of untreated ventricular fibrillation (VF), including the effects of epinephrine. DESIGN: Prospective, randomized, animal study. SETTING: Animal laboratory and university-affiliated research and educational institute. PARTICIPANTS: Domestic pigs. INTERVENTIONS: VF was induced in 20 anesthetized domestic pigs receiving mechanical ventilation. After 10 min of untreated VF, the animals were randomized. Defibrillation was attempted with up to three 150-J biphasic waveform shocks or a conventional sequence of 200-J, 300-J, and 360-J monophasic waveform shocks. When reversal of VF was unsuccessful, precordial compression was performed for 1 min, with or without administration of epinephrine. The protocol was repeated until spontaneous circulation was restored or for a maximum of 15 min. MEASUREMENTS AND RESULTS: No significant differences in the success of initial resuscitation or in the duration of survival were observed. However, significantly less impairment of myocardial function followed biphasic shocks. Administration of epinephrine reduced the total electrical energy required for successful resuscitation with both biphasic and monophasic waveform shocks. CONCLUSIONS: Lower-energy biphasic waveform shocks were as effective as conventional higher-energy monophasic waveform shocks for restoration of spontaneous circulation after 10 min of untreated VF. Significantly better postresuscitation myocardial function was observed after biphasic waveform defibrillation. Administration of epinephrine after prolonged cardiac arrest decreased the total energy required for successful resuscitation.     

Evolution of the stone heart after prolonged cardiac arrest

OBJECTIVES: We hypothesized that progressive impairment in diastolic function during cardiopulmonary resuscitation (CPR) precedes evolution of the "stone heart" after failure of CPR. We therefore measured sequential changes in left ventricular (LV) volumes and free-wall thickness of the heart during CPR in an experimental model. DESIGN: Prospective, observational animal study. SETTING: Medical research laboratory in an university-affiliated research and educational institute. SUBJECTS: Domestic pigs. METHODS: Ventricular fibrillation (VF) was induced in 40 anesthetized male domestic pigs weighing between 38 kg and 43 kg. After 4 min, 7 min, or 10 min of untreated VF, electrical defibrillation was attempted. Failing to reverse VF in each instance, precordial compression at a rate of 80/min was begun coincident with mechanical ventilation. Coronary perfusion pressures (CPPs) were computed from the differences in time-coincident diastolic aortic and right atrial pressures. Left ventricular (LV) systolic and diastolic ventricular volumes and thickness of the LV free wall were estimated with transesophageal echocardiography. The stroke volumes (SVs) were computed from the differences in decompression diastolic and compression systolic volumes. Free-wall thickness was measured on the hearts at autopsy. RESULTS: Significantly greater CPPs were generated with the 4 min of untreated cardiac arrest. Progressive reductions in LV diastolic and SV and increases in LV free-wall thickness were documented with increasing duration of untreated VF. A stone heart was confirmed at autopsy in each animal that failed resuscitative efforts. Correlations with indicator dilution method and physical measurements at autopsy corresponded closely with the echocardiographic measurements. CONCLUSION: Progressive impairment in diastolic function terminates in a stone heart after prolonged intervals of cardiac arrest.     

Employing vasopressin during cardiopulmonary resuscitation and vasodilatory shock as a lifesaving vasopressor

Epinephrine during cardiopulmonary resuscitation (CPR) is being discussed controversially due to its beta-receptor mediated adverse effects such as increased myocardial oxygen consumption, ventricular arrhythmias, ventilation-perfusion defect, postresuscitation myocardial dysfunction, ventricular arrhythmias and cardiac failure. In the CPR laboratory simulating adult pigs with ventricular fibrillation or postcountershock pulseless electrical activity, vasopressin improved vital organ blood flow, cerebral oxygen delivery, resuscitability, and neurological recovery better than did epinephrine. In paediatric preparations with asphyxia, epinephrine was superior to vasopressin, whereas in both paediatric pigs with ventricular fibrillation, and adult porcine models with asphyxia, combinations of vasopressin and epinephrine proved to be highly effective. This may suggest that a different efficiency of vasopressors in paediatric vs. adult preparations; and different effects of dysrhythmic vs. asphyxial cardiac arrest on vasopressor efficiency may be of significant importance. Whether these theories can be extrapolated to humans is unknown at this point in time. In patients with out-of-hospital ventricular fibrillation, a larger proportion of patients treated with vasopressin survived 24 h compared with patients treated with epinephrine; during in-hospital CPR, comparable short-term survival was found in groups treated with either vasopressin or epinephrine. Currently, a large trial of out-of-hospital cardiac arrest patients being treated with vasopressin vs. epinephrine is ongoing in Germany, Austria and Switzerland. The new CPR guidelines of both the American Heart Association, and European Resuscitation Council recommend 40 U vasopressin intravenously, and 1 mg epinephrine intravenously as equally effective for the treatment of adult patients in ventricular fibrillation; however, no recommendation for vasopressin was made to date for adult patients with asystole and pulseless electrical activity, and paediatrics due to lack of clinical data. When adrenergic vasopressors were unable to maintain arterial blood pressure in patients with vasodilatory shock, continuous infusions of vasopressin ( approximately 0.04 to approximately 0.1 U/min) stabilised cardiocirculatory parameters, and even ensured weaning from catecholamines.     

Myocardial dysfunction after resuscitation from cardiac arrest: An example of global myocardial stunning

Objectives. This study investigated the effect of prolonged cardiac arrest and subsequent cardiopulmonary resuscitation on left ventricular systolic and diastolic function.Background. Cardiac arrest from ventricular fibrillation results in cessation of forward blood flow, including myocardial blood flow. During cardiopulmonary resuscitation, myocardial blood flow remains suboptimal. Once the heart is defibrillated and successful resuscitation achieved, reversible myocardial dysfunction, or “stunning,” may occur. The magnitude and time course of myocardial stunning from cardiac arrest is unknown.Methods. Twenty-eight domestic swine (26 ± 1 kg) were studied with both invasive and noninvasive measurements of ventricular function before and after 10 or 15 min of untreated cardiac arrest. Contrast left ventriculograms, ventricular pressures, cardiac output, isovolumetric relaxation time (tau) and transthoracic Doppler-echocardiographic studies were obtained.Results. Twenty-three of 28 animals were successfully resuscitated and postresuscitation data obtained. Left ventricular ejection fraction showed a significant reduction 30 min after resuscitation (p < 0.05). Regional wall motion analysis revealed diffuse, global left ventricular systolic dysfunction. Left ventricular end-diastolic pressure increased significantly in the postresuscitation period (p < 0.05). Isovolumetric relaxation time (tau) was significantly increased over baseline by 2 h after resuscitation (p < 0.05). Similar findings were noted with the Doppler-echocardiographic analysis, including a reduction in fractional shortening (p <0.05), a reduction in mitral valve deceleration time (p < 0.05) and an increase in left ventricular isovolumetric relaxation time in 5 h after resuscitation (p < 0.05). By 24 h, these invasive and noninvasive variables of systolic and diastolic left ventricular function had begun to improve. At 48 h, all measures of left ventricular function had returned to baseline levels.Conclusions. Myocardial systolic and diastolic dysfunction is severe after 10 to 15 min of untreated cardiac arrest and successful resuscitation. Full recovery of this postresuscitation myocardial stunning is seen by 48 h in this experimental model of ventricular fibrillation cardiac arrest.     

Effect of optimizing the VV interval on left ventricular contractility in cardiac resynchronization therapy

Simultaneous biventricular pacing improves left ventricular (LV) function in patients with heart failure and LV asynchrony. Proper timing of the interventricular pacing interval (VV interval) may further optimize LV function. We investigated the acute hemodynamic response of changing the VV interval using maximum LV dP/dt (LV dP/dt_max) as a parameter for LV function. A biventricular pacemaker was implanted in 53 patients with severely impaired LV function, New York Heart Association class III and IV heart failure, left bundle branch block, LV asynchrony, and a QRS interval >150 ms. Optimization of the atrioventricular and VV intervals was based on measurement of LV dP/dt_max by a 0.014-in sensor-tipped pressure guidewire. Measurement of LV dP/dt_max was obtained without complications in all patients. In patients in sinus rhythm with ischemic cardiomyopathy or idiopathic dilated cardiomyopathy, mean improvements by simultaneous biventricular pacing were 17% and 18%, respectively. Patients in atrial fibrillation showed an improvement of 21%. Optimizing the VV interval resulted in further absolute increases of 8%, 7%, and 3%, respectively, in dP/dt_max in the 3 groups. Maximum dP/dt was achieved with LV pacing first in 44 patients, simultaneous right and left ventricular pacing in 6 patients, and right ventricular pacing first in 3 patients. The mean optimal VV intervals were 37 ± 32 ms in the atrial fibrillation group, 28 ± 30 ms in the idiopathic dilated cardiomyopathy group, and 52 ± 31 ms in the ischemic cardiomyopathy group. Optimization of the VV interval significantly increased LV dP/dt_max compared with simultaneous biventricular pacing, and such optimization could be easily, accurately, and reliably evaluated by a 0.014-in sensor-tipped pressure guidewire.     

Preservation of myocardial function by mechanical circulatory support during prolonged ischaemia.

The effect of mechanical circulatory support on left ventricular (LV) function was evaluated during prolonged myocardial ischaemia. Regional wall thickening of a normal and an ischaemic LV region were determined in eight calves (mean body weight 76 kg) using pairs of ultrasonic crystals. LV end-diastolic (mmHg) and peak systolic (mmHg) pressure as well as maximum dP/dt (mmHg s-1) were calculated from LV high-fidelity pressure tracings. The left circumflex coronary artery was ligated proximally for 6 h and reperfused for 18 h. Circulatory support by the assist device was performed from the beginning of ischaemia to the end of the experiment. After a mean time of 4 h all animals showed ventricular fibrillation, which was converted successfully in six animals after a mean time interval of 5 h. Five animals survived after 24 h. The non-surviving animals had larger infarcts, greater creatine kinase release and a larger drop in cardiac output during ischaemia. Haemodynamic measurements were carried out after turning off the assist device. Inotropic stimulation with 0.68 mg.min-1 dopamine i.v. was performed at the end of the study. LV regional function showed systolic bulging during myocardial ischaemia. After 18 h of reperfusion, the ischaemic wall recovered and showed normal systolic wall thickening in the presence of an increased LV preload. LV relaxation was prolonged after reperfusion, suggesting diastolic dysfunction. It is concluded that mechanical circulatory support is effective in protecting myocardial function during prolonged ischaemia in approximately two-thirds of the animals, despite severe ischaemic ventricular dysfunction and intermittent ventricular fibrillation.     

Cardiac functional and ultrastructural changes in early diabetic cardiomyopathy rabbits

Objectives It is not fully clarified how diabetes mellitus induced cardiac dysfunction and myocardial ultrastructural changes in the early state.In the present study,we provided an integrated approach to investigate early changes in myocardial function of diabetic rabbits and assessed the structural alteration.Methods and Results Diabetes was induced by alloxan injection.After 30 days,echocardio- graphy and left ventricular cannulation were performed in dia- betic(D,n=8) and control rabbits(C,n= 10).After catheterization, animals were killed for histological studies.Hema-toxylin -eosin and Masson’s Trichrome staining of the heart were analyzed.The ultrastructure of left ventricle was also examined with electron microscopy.Echocardiography revealed that early diabetic cardiomyopathy had impaired LV diastolic function expressed by diminished E-waves,increased Awaves, E/A ratio reversion and increased E-wave deceleration time(EDT).Concurrently,LV end-diastolic pressure(LVEDP) and diastolic time constant(T) were increased,minimum dP/ dt(LV-dp/dt)was reduced,obtained through cardiac catheterization.There were no significant differences in LV ejection fraction(EF),LV peak systolic pressure(LVSP), or maximum dP/dt(LV + dp/dt).Qualitative light microscopy revealed no histologic changes in myocardium from diabetic rabbits.The most evident ultrastructural change was spotted myofibrillar damage,while interstitial fibrosis was slight.Conclusions These results suggest that early diabetic cardiomyopathy in animal model is characterized by left ventricular diastolic dysfunction,both impaired active relaxation and increased passive chamber stiffness.Whereas,left ventricular systolic function can remain normal.It might partly contribute to myofibrillar damage,but not myocardial fibrosis.     

Abrogation of ventricular arrhythmias in a model of ischemia and reperfusion by targeting myocardial calcium cycling

Abnormal intracellular Ca(2+) cycling plays an important role in cardiac dysfunction and ventricular arrhythmias in the setting of heart failure and transient cardiac ischemia followed by reperfusion (I/R). We hypothesized that overexpression of the sarcoplasmic reticulum Ca(2+) ATPase pump (SERCA2a) may improve both contractile dysfunction and ventricular arrhythmias. Continuous ECG recordings were obtained in 46 conscious rats after adenoviral gene transfer of either SERCA2a or the reporter gene beta-galactosidase (beta gal) or parvalbumin (PV), as early as 48 h before and 48 h after 30 min ligation of the left anterior descending artery by using an implantable telemetry system. Sham-operated animals were used for comparison for hemodynamic measurements, whereas within-animal baseline was used for electrocardiographic and echocardiographic parameters. All episodes of nonsustained ventricular tachycardia (VT) and ventricular fibrillation (VF) were counted, and their durations were summed by telemetry. I/R decreased regional cardiac wall thickening as well as the maximal rate of left ventricular pressure rise (+dP/dt) and ventricular pressure fall (-dP/dt). SERCA2a restored regional wall thickening and +dP/dt and -dP/dt to levels seen preoperatively. Regional-wall motion and anterior-wall thickening were improved in the SERCA2a animals, as assessed by echocardiography and piezoelectric crystals. To assess whether these effects are SERCA2a specific, we overexpressed a skeletal-muscle protein, PV, to examine whether Ca(2+) buffering alone can mitigate ventricular arrhythmias. During the first hour after I/R, the rate of nonsustained VT plus VF was 16 +/- 5 episodes per h (n = 6) in the Ad.beta gal group, 22 +/- 6 in the Ad.PV group, and 4 +/- 2(n = 6, P < 0.01) in the Ad.SERCA2a group. The decrease in VT plus VF in the Ad.SERCA2a group was consistent throughout the 48 h of monitoring. These results show that improving intracellular Ca(2+) handling by overexpression of SERCA2a restores contractile function and reduces ventricular arrhythmias during I/R.     

Nitroprusside infusion in experimental acute myocardial infarction with systemic hypertension: effects on systemic hemodynamics and regional myocardial blood flows

The effects of graded doses of nitroprusside on regional myocardial blood flow were studied in awake, acutely hypertensive dogs with acute myocardial infarction. Acute systemic hypertension was produced by infusing a mixture of norepinephrine and epinephrine for 80 minutes after coronary artery occlusion. The increase in aortic pressure produced by catecholamine infusion was accompanied by increases in heart rate, left ventricular (LV) end-diastolic pressure, first derivative of LV pressure (dP/dt), dP/dt at an LV developed pressure of 50 mm Hg (dP/dt/P) and pressure-rate product, but total peripheral vascular resistance did not change significantly. Two graded doses of nitroprusside were then infused, each for 25 minutes, beginning 30 minutes after the onset of coronary artery occlusion. The smaller dose of nitroprusside returned aortic pressure to control levels and significantly reduced total peripheral vascular resistance and LV end-diastolic pressure, but did not affect cardiac output, heart rate, LV dP/dt, dP/dt/P and pressure-rate product. Regional blood flow increased to both the ischemic and normal myocardium. The larger dose of nitroprusside further reduced aortic pressure and total peripheral vascular resistance and LV end-diastolic pressure and significantly increased heart rate and cardiac output. However, LV dP/dt, dP/dt/P and pressure-rate product remained unchanged. Regional blood flow to normal myocardium increased, but the increase in ischemic endocardial blood flow produced by the smaller dose of nitroprusside was no longer significant when the larger dose was administered. These changes were not produced by administration of normal saline solution.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of heparin and protamine on left ventricular performance in the dog.

The effects of protamine on left ventricular (LV) function were measured under conditions of controlled heart rate and proximal aortic pressure in eight anaesthetized, heparinised dogs. Protamine 3 mg.kg-1 produced a 21% decrease in LV dP/dt max, a 43% decrease in cardiac output, a 47% decrease in stroke work and decreases in systolic and diastolic pressures (-16%, -19% respectively). Protamine 6 mg.kg-1 resulted in a 17% decrease in LV dP/dt max, a 26% decrease in cardiac output, a 50% decrease in LV stroke work and 25 and 30% decreases in systolic and diastolic pressures. These results show that an impairment of LV function plays an important part in the circulatory depression produced by protamine.     

Basal inotropic state in rats with renal hypertension: influence of coronary flow and perfusion pressure

Cardiac performance in renal hypertensive animals has been variously reported as normal, increased, or decreased. Because of the many factors that can alter cardiac function in vivo ventricular contractility was investigated in isolated, paced, isovolumic heart preparations (modified Langendorff). Twenty one hypertensive rats (2 kidney, 1 clip Goldblatt) and 21 matched sham operated controls, were studied. Mean(SD) blood pressure and left ventricular weight were significantly higher in the study rats (228(5) vs 125(2) mmHg and 4.16(0.12) vs 2.35(0.04) mg X kg-1 respectively). In the first experiment performed at 50 mmHg perfusion pressure left ventricular +dP/dt and myocardial flow rate were lower in 12 study rats (mean(SD) 1782(79) vs 2270(105) mmHg X s-1, 5.8(0.4) vs 14.0(1.0) ml X g-1 LV weight X min-1, respectively) than in the controls. In a second experiment performed at 80 mmHg perfusion pressure (nine study hearts and seven controls) the increased myocardial flow rate resulted in a higher left ventricular +dP/dt in both groups, but the study hearts still had a lower mean(SD) myocardial flow rate than the controls (12.5(0.9) vs 19.8(2.2) ml X g-1 LV weight X min-1; the difference in left ventricular +dP/dt became non-significant (2646(186) vs 2951(136) mmHg X s-1). Similarly, at equal myocardial flow rates (study hearts at 80 mmHg perfusion pressure and controls at 50 mmHg perfusion pressure) ventricular performance was similar in the two groups (mean(SD) left ventricular +dP/dt 2270(105) in controls vs 2646(186) mmHg X s-1 in study hearts).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of fluorocarbons with and without oxygen supplementation on cardiac hemodynamics and energetics

Because of uncertainty about the mechanism by which fluorocarbons ameliorate myocardial ischemia, the effects of a fluorocarbon emulsion, perfluorodecalin and perfluorotripropylamine (Fluosol-DA 20% TM) with and without 100% O2 inhalation, on cardiac hemodynamics and energetics were studied in the anesthetized dog. Left ventricular (LV) intramural partial pressure of oxygen (PmO2) was measured by mass spectrometry before and after intravenous infusion of Fluosol-DA 20% (40 ml/kg), and was compared with measurements made in another group of dogs receiving the volume expander dextran (36 ml/kg). Both groups of dogs were then ventilated with 100% O2 and repeat measurements were performed. In the 11 animals receiving fluorocarbons, there were increases in left atrial pressure, LV myocardial blood flow, and LV myocardial O2 consumption (MVO2) compatible with volume expansion. After 100% O2, LV MVO2 decreased to control values, while PmO2 increased to 127 +/- 48 mm Hg (p less than 0.001). There were no significant changes in heart rate, arterial pressure or first derivative of LV pressure (dP/dt) during the study. In 10 dogs treated with dextran there was no change in heart rate or dP/dt, but arterial and left atrial pressures were higher after dextran infusion and remained elevated after 100% O2 inhalation. LV MVO2 increased with volume expansion, and remained increased after 100% O2. PmO2 (66 +/- 18 mm Hg) after 100% O2 was lower (p less than 0.02) than in the fluorocarbon-treated dogs after O2 inhalation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Regional and global biventricular function during dipyridamole stress testing

This study assesses the relation between regional ventricular performance (using 2-dimensional echocardiography) and global systolic and diastolic indexes of biventricular myocardial function (using hemodynamic monitoring) during dipyridamole stress testing. Simultaneous 2-dimensional echocardiographic and biventricular hemodynamic monitoring during dipyridamole infusion (0.56 mg/kg over 4 minutes) was performed in 19 patients. All patients had a normal resting function. Eleven of the 19 patients had a positive echocardiography test (new wall motion dyssynergy with dipyridamole) and they formed group 1. Eight patients had a negative echocardiography test (group 2). During baseline conditions, no significant differences were found in the 2 groups: rate pressure product (107 +/- 16 vs 108 +/- 13 mm Hg x beats/min x 1/100), positive left ventricular (LV) dP/dt (1,950 +/- 473 vs 2,262 +/- 430 mm Hg/s), negative LV dP/dt (-2,069 +/- 620 vs -2,205 +/- 245), LV end-diastolic pressure (8.2 +/- 4.4 vs 9.6 +/- 4.0 mm Hg), right ventricular positive dP/dt (368 +/- 133 vs 400 +/- 190 mm Hg/s) and negative dP/dt (-281 +/- 89 vs -383 +/- 147). At peak dipyridamole, the 2 groups were different for LV end-diastolic pressure (20 +/- 10 vs 8 +/- 5 mm Hg, p less than 0.01), LV positive dP/dt (2,100 +/- 688 vs 3,013 +/- 851 mm Hg/s, p less than 0.01) and negative dP/dt (-1,868 +/- 518 vs -2,564 +/- 272, p less than 0.01). At peak ischemia, LV positive dP/dt increased slightly, but not significantly, while negative dP/dt decreased significantly (p less than 0.01) in comparison with resting values.(ABSTRACT TRUNCATED AT 250 WORDS)     

Features of cardiac arrest episodes with and without acute myocardial infarction in the Coronary Artery Surgery Study (CASS)

Angiographic evidence of coronary artery disease was present in 16,002 patients in the Coronary Artery Surgery Study (CASS) registry. Of these patients, 551 had a history of cardiac arrest before enrollment angiography. Cardiac arrest was a complication of acute myocardial infarction (AMI) in 372 patients (68%). Electrocardiographic documentation of the responsible rhythm was available in 283 patients. Ventricular fibrillation (VF) was present in 112 (60%), ventricular tachycardia (VT) in 41 (22%) and both VT and VF in 26 (14%) patients. Stepwise linear discriminant analysis comparing the 551 cardiac arrest patients with the other 15,451 patients selected left ventricular wall motion score (F = 265), use of digitalis (F = 71), impaired blood supply to any segment (F = 16) and particularly to the anterior wall (F = 11) as discriminating variables associated with cardiac arrest. Patients with cardiac arrest occurring as a complication of AMI were younger (F = 12), had greater impairment of coronary blood supply (F = 7) and were more likely to be on a cholesterol-lowering diet (F = 16) than were patients with arrest remote from infarction. Comparison of patients with VT versus those with VF showed a positive association of VT with age (F = 8), a trend toward worse left ventricular function and presence of a left ventricular aneurysm, but no difference in severity and collateralization of coronary artery disease. It is concluded that cardiac arrest is related to the extent of myocardial damage.(ABSTRACT TRUNCATED AT 250 WORDS)     

Monophasic versus biphasic transthoracic countershock after prolonged ventricular fibrillation in a swine model

OBJECTIVE: We sought to compare the defibrillation efficacy of a low-energy biphasic truncated exponential (BTE) waveform and a conventional higher-energy monophasic truncated exponential (MTE) waveform after prolonged ventricular fibrillation (VF). BACKGROUND: Low energy biphasic countershocks have been shown to be effective after brief episodes of VF (15 to 30 s) and to produce few postshock electrocardiogram abnormalities. METHODS: Swine were randomized to MTE (n = 18) or BTE (n = 20) after 5 min of VF. The first MTE shock dose was 200 J, and first BTE dose 150 J. If required, up to two additional shocks were administered (300, 360 J MTE; 150, 150 J BTE). If VF persisted manual cardiopulmonary resuscitation (CPR) was begun, and shocks were administered until VF was terminated. Successful defibrillation was defined as termination of VF regardless of postshock rhythm. If countershock terminated VF but was followed by a nonperfusing rhythm, CPR was performed until a perfusing rhythm developed. Arterial pressure, left ventricular (LV) pressure, first derivative of LV pressure and cardiac output were measured at intervals for 60 min postresuscitation. RESULTS: The odds ratio of first-shock success with BTE versus MTE was 0.67 (p = 0.55). The rate of termination of VF with the second or third shocks was similar between groups, as was the incidence of postshock pulseless electrical activity (15/18 MTE, 18/20 BTE) and CPR time for those animals that were resuscitated. Hemodynamic variables were not significantly different between groups at 15, 30 and 60 min after resuscitation. CONCLUSIONS: Monophasic and biphasic waveforms were equally effective in terminating prolonged VF with the first shock, and there was no apparent clinical disadvantage of subsequent low-energy biphasic shocks compared with progressive energy monophasic shocks. Lower-energy shocks were not associated with less postresuscitation myocardial dysfunction.     

Force-frequency relationship as a predictor of long-term prognosis in patients with heart diseases

Adequate evaluation of the nature of the residual failing myocardium, as well as the severity of myocardial injury, is important for managing patients with heart failure. The aim of this study was to investigate the myocardial function and the prognosis of patients with heart diseases using the force-frequency relationship (FFR). We enrolled 76 patients with sinus rhythm who had miscellaneous heart diseases and performed incremental right atrial pacing at the time of diagnostic cardiac catheterization. The first derivatives of left ventricular pressure (dP/dt) were recorded using a micro manometer-tipped catheter during the study. To represent properties of FFR, two parameters-the peak force rate (PFR) and force gain (FG)-were estimated. PFR was defined as the heart rate at which dP/dt became maximum. FG was defined as the difference between dP/dt at PFR and dP/dt at the basal heart rate. FG decreased as the severity of left ventricular (LV) dysfunction increased (372.0 ± 110.7, 209.5 ± 29.1 and 116.3 ± 13.1 mmHg/s for normal LV function, mild LV dysfunction and severe LV dysfunction groups, P < 0.05, respectively). PFR correlated with cardiac index (r = 0.375, P = 0.001). FG correlated with LV end systolic volume index (r = -0.297, P = 0.010) and LV ejection fraction (r = 0.539, P < 0.001). Furthermore, pulmonary arterial wedge pressure [hazard ratio (HR) 1.126, P < 0.01] and FG (HR 0.992, P = 0.061) tended to be independent predictors for cardiovascular death. Analysis of FFR, especially FG, seems to be useful to evaluate the nature of the failing myocardium and the prognosis of patients with heart diseases.     

Potential use of isovolumic contraction velocity in assessment of left ventricular contractility in man: A simultaneous pulsed Doppler tissue imaging and cardiac catheterization study.

AIMS: Echocardiographic techniques have so far provided suboptimal estimates of myocardial contractility in humans. Longitudinal myocardial motion during the isovolumic contraction (IVC) phase, measured by colour tissue Doppler imaging (TDI), has recently been shown in experimental animal models to reflect the state of myocardial contractility. The aim of the present study was to investigate the relationship between left ventricular (LV) isovolumic contraction velocities (IVCv) using pulsed Doppler tissue imaging (DTI) and global LV contractility as measured during cardiac catheterization. METHODS AND RESULTS: Cardiac catheterization and pulsed DTI were simultaneously performed in 16 consecutive patients (13 males, mean age 55+/-10years) with a variety of cardiac diseases. Relationships between the peak positive IVCv as measured at basal levels of the lateral, septal, anterior and posterior walls and the first derivative of LV pressure (+dP/dt(max)), were investigated. Peak IVCv measurements were obtainable in 81-100% of the four LV wall segments. Statistically significant linear relationships were found between IVCv and +dP/dt(max) at the lateral (r=0.58, P<0.05), septal (r=0.66, P<0.01), anterior (r=0.73, P<0.01) and posterior (r=0.81, P<0.001) segments of the LV. CONCLUSION: IVCv of the basal four LV walls correlates strongly with peak +dP/dt. IVCv is a readily obtainable non-invasive parameter, which correlates with the classical invasive measurement of global LV contractility. It appears likely that there are regional differences in wall motion when DTI is used to determine state of LV contractility.     

Reduced cardiac reserve in amiodarone-treated pigs after cardiopulmonary bypass and cardioplegic arrest.

An animal model was designed for blinded study to elucidate whether cardiac pump failure after heart surgery in amiodarone-treated patients is due to interference between the drug and the surgical procedures. Seventeen adult pigs were treated with amiodarone for 30 days (study animals, 1,400 mg/day, n = 9; untreated control animals, n = 8) followed by exposure to cardiopulmonary bypass and topical cold cardioplegic arrest (Bretschneiders solution) for 60 min. Apart from 1 g of calcium, no inotropic agents were administered. Cardiac reserve was tested by ventricular pacing (200 beats/min for 30 min or until exhaustion). No difference in hemodynamic status was observed between the treated and the untreated group before pacing. Pacing duration in the amiodarone-treated pigs was 10 +/- 3 versus 22 +/- 4 min in control pigs (p less than 0.05). Only one amiodarone-treated pig survived 30 min of pacing compared with five control pigs (11% vs. 63%, p less than 0.05). The following variables differed significantly in the two groups during pacing: cardiac output, left ventricular pressure, arterial pressure and peak positive and negative first derivative of left ventricular pressure (dP/dt). Most marked were the changes in peak positive dP/dt, indicating a compromised systolic function. The two groups did not differ in preload or afterload at any time during the experiments.