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R J Gazmuri

Publications and source records attributed to R J Gazmuri.

At least 19 recordsLinked to original sources
PubMed2001

Successful ventricular defibrillation by the selective sodium-hydrogen exchanger isoform-1 inhibitor cariporide.

BACKGROUND: Sodium-hydrogen exchanger isoform-1 (NHE-1) activation worsens functional myocardial abnormalities associated with ischemia and reperfusion. We hypothesize that these abnormalities may limit cardiac resuscitation from ventricular fibrillation (VF) and investigated whether NHE-1 inhibition with the benzoylguanidine derivative cariporide could improve resuscitability, postresuscitation myocardial function, and short-term survival in isolated heart and intact rat models of VF. Methods and Results-- In the isolated rat heart, VF was induced for 25 minutes. Perfusion was interrupted for the initial 10 minutes and restarted at 10% of baseline flow for the remaining 15 minutes (simulating chest compression). Cariporide ameliorated ischemic contracture, prevented postresuscitation diastolic dysfunction, and favored earlier return of contractile function. In the intact rat, cariporide, injected into the right atrium before chest compression was started (after 6 minutes of untreated VF), prompted spontaneous defibrillation between minutes 7 and 9 of chest compression in 6 of 8 rats. In contrast, electrical defibrillation was required in each of 8 control rats after completion of a predetermined 16-minute interval of VF. After resuscitation, cariporide-treated rats had less ventricular ectopic activity and normalized their hemodynamic function faster. Electrical defibrillation was then timed in control rats to match the time when spontaneous defibrillation occurred in cariporide-treated rats. With comparable VF duration, postresuscitation hemodynamic dysfunction was ameliorated by cariporide, but only when more severe ischemia was modeled by prolongation of the interval of untreated VF from 6 to 10 minutes. CONCLUSION: NHE-1 inhibition may represent a novel and remarkably effective intervention for resuscitation from VF.

Animals↗
PubMed2001

Myocardial protection during ventricular fibrillation by reduction of proton-driven sarcolemmal sodium influx.

Although the inhibition of proton-driven sarcolemmal sodium influx ameliorates ischemic injury in the quiescent myocardium, the effects when ventricular fibrillation is present are largely unknown. We used an isolated rat heart model to investigate whether inhibition of the sodium-hydrogen exchanger isoform-1 (with the benzoylguanidine derivatives HOE-694 and cariporide) with or without concomitant inhibition of the sodium-bicarbonate co-transporter (with perfusate buffered with N-2-hydroxyethylpiperazine-N-2-ethanesulfonic acid [HEPES]) during ischemia and ventricular fibrillation could ameliorate functional myocardial abnormalities presumed to limit cardiac resuscitability. Ischemic contracture, which typically develops during ventricular fibrillation, was ameliorated by HOE-694 when either a bicarbonate-buffered (20 +/- 7 mm Hg vs 15 +/- 5 mm Hg, P <.05) or a HEPES-buffered (14 +/- 5 mm Hg vs 10 +/- 3 mm Hg, P <.04) perfusate was used. Maximal amelioration occurred when cariporide and HEPES-buffered perfusate were used simultaneously (25 +/- 14 mm Hg vs 11 +/- 3 mm Hg, P <.01), and this was accompanied by lesser leftward shifts of the end-diastolic pressure-volume curves after defibrillation. Intramyocardial sodium increases of 76% during ischemia and ventricular fibrillation (P <.05) were ameliorated by the sodium-influx-limiting interventions. Thus interventions limiting sarcolemmal sodium influx during ischemia and ventricular fibrillation may facilitate successful resuscitation from ventricular fibrillation.

Animals↗
PubMed2000

Myocardial effects of repeated electrical defibrillations in the isolated fibrillating rat heart.

OBJECTIVE: Although substantial myocardial cell injury has been reported after high-energy electrical defibrillation, only minimal injury with transient functional defects seems to develop at energy levels not exceeding those required to reverse ventricular fibrillation. Because multiple electrical shocks are often delivered in clinical settings during attempts to reverse ventricular fibrillation, we investigated the effects of repetitive shocks on postresuscitation myocardial dysfunction by using an isolated rat heart model of ventricular fibrillation. DESIGN: Prospective and randomized. SETTING: Cardiopulmonary resuscitation research laboratory. SUBJECTS: Twenty-seven Sprague-Dawley rats. INTERVENTIONS: Hearts were harvested and perfused at a constant flow of 10 mL/min by using a modified Krebs-Henseleit solution equilibrated with 95% oxygen and 5% CO2. Ventricular fibrillation (VF) was induced by a 0.05-mA current delivered to the right ventricular endocardium and the perfusate flow was stopped. After 10 mins, the perfusate flow was resumed at 20% of baseline flow and maintained for 15 additional minutes before returning to baseline flow after 25 mins of VF (VF25 mins). Twenty-seven hearts were randomized to receive from VF22 mins to VF25 mins either 0 epicardial shocks, 6 epicardial shocks, or 12 epicardial shocks. MEASUREMENTS AND MAIN RESULTS: Isovolumic indices of left ventricular function were obtained by using a latex balloon advanced through the mitral valve into the ventricular cavity. After defibrillation, indices of contractile function rapidly returned to baseline without differences among groups. The isovolumic end-diastolic pressure, however, remained elevated throughout the postresuscitation interval. A left shift of the diastolic pressure-volume curves without changes in their slope was observed at 10 mins after resuscitation with partial return to baseline by 30 mins postresuscitation. The shifts were significantly greater in hearts that received 12 shocks. CONCLUSIONS: These findings indicate that repetitive low-energy electrical shocks do not accentuate postischemic systolic dysfunction in the isolated fibrillating rat heart but adversely affect postischemic diastolic dysfunction by reducing the unstressed left ventricular end-diastolic volume.

Animals↗
PubMed2000

Effects of repetitive electrical shocks on postresuscitation myocardial function.

Whereas myocardial cell injury can occur during electrical defibrillation proportional to the energy level of individual shocks, only minimal (or no) injury seems to develop when the energy is limited to the levels typically required to terminate ventricular fibrillation. During cardiac arrest, however, multiple shocks are often required to terminate ventricular fibrillation or to treat episodes that appear subsequently during the resuscitation effort or the postresuscitation interval. Concern exists because an inverse relationship has been reported between the number of electrical shocks delivered during cardiac resuscitation and both resuscitability and survival. Repetitive electrical shocks can alter diastolic function and prompt leftward shifts of the end-diastolic pressure-volume curves. Repetitive shocks may, therefore, contribute to the recently recognized phenomenon of postresuscitation myocardial dysfunction and hamper efforts to reestablish competent myocardial function after resuscitation. Thus, strategies aimed at limiting the number of electrical shocks during cardiopulmonary resuscitation are highly desirable. These may include real-time ventricular fibrillation waveform analysis to improve targeting of individual shocks and efforts (using mechanical and pharmacologic means) to render the myocardium more responsive to individual shocks and to promote greater electrical stability after successful defibrillation.

Animals↗
PubMed1999

Myocardial effects of ventricular fibrillation in the isolated rat heart.

OBJECTIVE: Ventricular fibrillation (VF) is known to increase myocardial oxygen requirements and to alter coronary vascular physiology. However, the significance of these effects during cardiac arrest and resuscitation is not well understood. A model was developed in the isolated rat heart to investigate the myocardial effects of VF during a simulated episode of cardiac arrest and resuscitation. We hypothesized that VF would intensify the severity of myocardial ischemia and consequently accentuate postischemic myocardial dysfunction. DESIGN: Prospective and randomized. SETTING: Research laboratory. SUBJECTS: Twenty Sprague-Dawley rats. INTERVENTIONS: Hearts were harvested and perfused at a constant flow rate of 10 mL/min using a modified Krebs-Henseleit solution equilibrated with 95% oxygen and 5% CO2. In five hearts, VF was induced by a 0.05-mA current delivered to the right ventricular endocardium. The perfusate flow was then stopped for a 10-min interval and resumed at 20% of baseline flow for another 10 mins. After 20 mins of VF, the perfusate flow was returned to baseline and a sinus rhythm reestablished by epicardial electrical shocks. The studies were randomized and included three additional groups to control for the effects of ischemia without VF (n = 5), the effects of VF without ischemia (n = 5), and the stability of the preparation (n = 5). MEASUREMENTS AND MAIN RESULTS: Isovolumic indices of left ventricular function were obtained using a latex balloon advanced through the mitral valve and distended to an end-diastolic pressure of 10 mm Hg. The coronary effluent was collected from the right ventricular cavity. VF during myocardial ischemia was associated with a higher coronary effluent PCO2, increased coronary vascular resistance, and development of ischemic contracture as indicated by increases in left ventricular pressure from 9+/-3 to 33+/-6 mm Hg (p < .05). After defibrillation, contractility and relaxation rapidly returned to baseline values, whereas the isovolumic end-diastolic pressure remained elevated for 20 mins. These changes were much less prominent when ischemia was not accompanied by VF. CONCLUSIONS: These findings indicate that VF may adversely affect myocardial ischemia by hastening the development of ischemic contracture, increasing coronary vascular resistance, and favoring the development of diastolic pump failure early after resuscitation from cardiac arrest.

Animals↗
PubMed1996

Myocardial dysfunction after successful resuscitation from cardiac arrest.

OBJECTIVE: To investigate the functional and metabolic changes in the myocardium after successful resuscitation from cardiac arrest. DESIGN: Prospective, randomized, sham-controlled study. SETTING: Animal laboratory at a university center. SUBJECTS: Domestic pigs. INTERVENTIONS: Electric induction of ventricular fibrillation by alternating current delivered to the right ventricular endocardium through a pacing electrode. Electric defibrillation was attempted after an interval of 12 mins of ventricular fibrillation, which included 4 mins of untreated ventricular fibrillation and 8 mins of precordial compression in 13 animals, seven of which were successfully resuscitated. Seven additional animals were randomized to serve as "sham" controls, in which cardiac arrest was not induced. MEASUREMENTS AND MAIN RESULTS: Left ventricular pressure-volume relationships utilizing the conductance method were obtained in conjunction with conventional hemodynamic and metabolic measurements at baseline and during a 6-hr interval after successful cardiac resuscitation. Progressive and striking increases in left ventricular volumes were observed after successful cardiac resuscitation. The end-diastolic volume increased from a prearrest level of 89 +/- 21 mL to a maximum of 154 +/- 53 mL (p<.05) at 360 mins after successful resuscitation. The time-coincident end-systolic volume increased from 54 +/- 21 to 126 +/- 54 mL (p<.05), such that the ejection fraction was reduced from 0.41 +/- 0.10 to 0.20 +/- 0.07 ( p<.05). Ventricular dilation was associated with marked reductions in stroke volume and ventricular work. However, compensatory increases in heart rate maintained cardiac output at levels that sustained adequate systemic oxygen delivery. The slope of the end-systolic pressure-volume relationships progressively decreased from 5.04 +/- 1.88 to 2.00 +/- 0.57 mm Hg/mL (p<.05) at 360 mins after successful resuscitation. The volume intercept at left ventricular pressure of 100 mm Hg increased from 43 +/- 19 to 94 +/- 51 mL (p=.03). Both the decrease in the slope and the increase in the volume intercept were characteristic of progressive impairment in contractile function. The rate of left ventricular pressure decrease was unchanged. Accordingly, no substantial changes in lusitropic properties were identified. Despite large increases in end-diastolic volume, the end-diastolic pressure remained unchanged. CONCLUSION: Postresuscitation myocardial dysfunction in this animal model was characterized by impaired contractile function, decreased work capability, and ventricular dilation.

Animals↗
PubMed1995

Epinephrine increases the severity of postresuscitation myocardial dysfunction.

BACKGROUND: Epinephrine has been the mainstay for cardiac resuscitation for more than 30 years. Its vasopressor effect by which it increases coronary perfusion pressure is likely to favor initial resuscitation. Its beta-adrenergic action, however, may have detrimental effects on postresuscitation myocardial function when administered before resuscitation because it increases myocardial oxygen consumption. In the present study, our focus was on postresuscitation effects of epinephrine when this adrenergic agent was administered during cardiopulmonary resuscitation. Postresuscitation myocardial functions were compared with those of a selective alpha-adrenergic agent, phenylephrine, when epinephrine was combined with a beta 1-adrenergic blocking agent, esmolol, and saline placebo. METHODS AND RESULTS: Ventricular fibrillation was induced in 40 Sprague-Dawley rats. Mechanical ventilation and precordial compression was initiated either 4 or 8 minutes after the start of ventricular fibrillation. The adrenergic drug or saline placebo was administered as a bolus after 4 minutes of precordial compression. Defibrillation was attempted 4 minutes later. Left ventricular pressure, dP/dt40, and negative dP/dt were continuously measured for an interval of 240 minutes after successful cardiac resuscitation. Except for saline placebo, comparable increases in coronary perfusion pressure were observed after each drug intervention. The number of countershocks required for restoration of spontaneous circulation was significantly greater for epinephrine-treated animals (10 +/- 8) when compared with phenylephrine-treated animals (1.8 +/- 0.4, P < .01) and with animals treated with epinephrine combined with esmolol (1.6 +/- 0.9, P < .01). After resuscitation, dP/dt40 and negative dP/dt were significantly decreased and left ventricular end-diastolic pressure was significantly increased in each animal when compared with prearrest levels. However, the greatest impairment followed epinephrine, and this was associated with significantly greater heart rate and the shortest interval of postresuscitation survival of 8 +/- 4 hours, whereas placebo controls survived for 12 +/- 11 hours. Phenylephrine-treated animals survived for 41 +/- 10 hours (P < .01 versus epinephrine), and animals that received a combination of epinephrine and esmolol survived for 35 +/- 11 hours (P < .01 versus epinephrine). When the duration of untreated cardiac arrest was increased from 4 to 8 minutes, the severity of postresuscitation left ventricular dysfunction was magnified, but disproportionate decreases in postresuscitation survival were again observed with placebo and epinephrine when compared with alpha-adrenergic agonists. CONCLUSIONS: In an established rodent model after resuscitation following cardiac arrest, epinephrine significantly increased the severity of postresuscitation myocardial dysfunction and decreased duration of survival. More selective alpha-adrenergic agonist or blockade of beta 1-adrenergic actions of epinephrine reduced postresuscitation myocardial impairment and prolonged survival.

Adrenergic Agonists↗
PubMed1995

Effect of arrest time on the hemodynamic efficacy of precordial compression.

OBJECTIVES: To evaluate the efficacy of conventional threshold levels of coronary perfusion pressure and end-tidal CO2 as predictors of resuscitability after prolonged cardiac arrest. DESIGN: Prospective, randomized, controlled animal study. SETTING: University research laboratory. SUBJECTS: Twenty-one Sprague-Dawley rats, including three groups of seven animals in each group. INTERVENTIONS: Ventricular fibrillation was untreated for 9, 12, or 15 mins. After an additional 5-min interval of precordial compression, external direct current defibrillation was attempted. MEASUREMENTS AND MAIN RESULTS: All animals were successfully resuscitated after 9 mins of ventricular fibrillation but less than one half of the animals were successfully resuscitated after 15 mins of ventricular fibrillation. Each of seven animals survived for 24 hrs after 9 mins of untreated ventricular fibrillation but none of the animals survived after 15 mins of ventricular fibrillation. In this experimental setting, neither coronary perfusion pressure nor end-tidal CO2 produced by precordial compression was predictive of outcomes when the animals underwent progressively longer intervals of untreated cardiac arrest. CONCLUSIONS: The efficacy of precordial compression--as measured by coronary perfusion pressure and end-tidal CO2 concentration after prolongation of untreated cardiac arrest--was not overtly compromised. However, the previously established critical threshold levels of coronary perfusion pressure and end-tidal CO2 failed as predictors of resuscitability after prolonged intervals of untreated cardiac arrest.

Animals↗
PubMed1994

Spontaneous gasping increases the ability to resuscitate during experimental cardiopulmonary resuscitation.

OBJECTIVE: To evaluate the effect of spontaneous gasping on cardiorespiratory functions and the ability to resuscitate during experimental cardiac arrest. DATA SOURCES: Studies in rat and pig models during cardiac arrest and cardiopulmonary resuscitation (CPR). STUDY SELECTION: We retrospectively examined the role of spontaneous gasping during the course of experimental studies on cardiopulmonary resuscitation. DATA EXTRACTION: The data were extracted to illustrate the mechanisms of spontaneous gasping and its effects on pulmonary gas exchange and blood circulation during CPR. DATA SYNTHESIS: Spontaneous gasping increased PaO2 and decreased PaCO2 values during precordial compression in the absence of mechanical ventilation. The frequency of gasping during precordial compression was greater in successfully resuscitated animals. A significant linear correlation was established between coronary artery perfusion pressure and both the frequency (r2 = .90, p < .01) and the duration (r2 = 0.69, p < .01) of gasping during untreated ventricular fibrillation and before resuscitation was attempted. Like coronary perfusion pressure, the frequency and duration of gasping predicted the success of cardiac resuscitation attempts. CONCLUSIONS: Spontaneous gasping is associated with both pulmonary and hemodynamic effects during cardiac arrest in experimental animals. Spontaneous gasping is biologically useful and is predictive of a more favorable outcome of resuscitative efforts.

Animals↗