EXPERIMENTAL STUDIES
Effects of Alcohol on Cardiovascular Experimental
Nonpenetrating
A. JAMES LIEDTKE, MD WILLIAM E. DeMUTH, MD Hershey,
Pennsylvania
From the Departments of Medicine and Surgery, Divisions of Cardiology and Cardiothoracic Surgery, Pennsylvania State University College of Medicine and The Milton S. Hershey Medical Center, Hershey, Pa. Manuscript accepted June 12, 1974. Address for reprints: A. James Liedtke, MD. Division of Cardiobgy, Department of Medicine, The Mifton S. Hershey Medical Center, Hershey, Pa. 17033.
Performance
After
Chest Trauma
Electrocardiographic and hemodynamic correlates were recorded before and afler a standardized nonpenetrating blow to the chest in 9 anesthetized control dogs (Group I), 5 dogs pretreated with alcohol, 0.4 g/kg intravenously (Group II), and 12 dogs undergolng chest trauma afler alcohol infusions (Group Ill). In animals in Group I, transient major arrhythmias, including complete heart block and ventricular tachycardia, occurred immediately afler impact. One animal died with ventricular fibrillation. In the eight survivors these disturbances were accompanied by acute reductions in aortic pressure and cardiac index; values for both variables gradually increased after restoration of sinus mechanism. Alcohol alone (Group II) produced no significant alterations in either hemodynamic performance or electrical activity, but when combined with nonpenetrating chest injury (Group Ill) it caused a mortality rate of 92 percent, the majority of animals dying with electromechanical dissociation. Mean survival time in Group Ill was 23.1 f 6.5 (standard error of the mean) minutes compared with 60.3 f 9.6 minutes in Group I. At autopsy, minor cardiac lesions of either the pericardium or myocardium were observed in all animals in Groups I and Ill, but none were considered lethal. It is concluded that administration of alcohol, even in small doses, can effect catastrophic reductions in mechanical performance in the presence of otherwise nonfatal cardiac injury secondary to nonpenetrating chest trauma. The clinical implications of this association are discussed.
Previous studies from this laboratory’,2 have demonstrated in a canine model system that nonpenetrating chest trauma causes major changes in left ventricular performance. Traffic accident statistics indicate that such trauma can occur in man, usually after violent contact with the steering column and other fixed automobile accessories in a high speed collision. Such injuries represent a leading cause of death, particularly in younger age groups.3s4 Data from several agencies5 have strongly incriminated excess alcohol intake as a precipitating factor in such fatalities, and alcohol has been shown to have direct pharmacologic effects on the h >art, including both stimulationslo and depression11-20 of m ec h anical performance, inducement of electrical pacemaker asystole and cardiac arrest,2,7,g and a depression in peripheral vasomotor tone, resulting in increased susceptibility to trauma and shock.12JS To date, the specific effects of alcohol on the cardiovascular system after nonpenetrating chest trauma have not been defined. In this study we evaluated and compared several indexes of cardiac performance in response to chest trauma and alcohol, considered both selectively and in combination, in the canine model system previously described.
February 1975
The American Journal of CARDIOLOGY
Volume 35
243
ALCOHOL AND CHEST TRAUMA-LIEDTKE
AND DeMUTH
Methods Twenty-six mongrel dogs, weighing 8.4 to 26.0 kg (average 16.3), were anesthetized with intravenously administered pentobarbital (15 mg/kg body weight) and, after cuffed endotracheal intubation, maintained with methoxyflurane and oxygen under conditions of controlled ventilation. Determinations of arterial pH, and partial pressures of oxygen (PO,) and carbon dioxide (PCOz) and carbon dioxide combining power were obtained throughout the studies to assure adequacy of ventilation and acid-base balance. Animals were secured firmly in the supine position as described previously.1*2 Polyethylene catheters (inner diameter 0.125 inch) were placed in the superior vena cava or right atrium by way of the right jugular vein, and into the aorta by cannulation of a femoral artery. Each catheter was connected to a P23DB Statham pressure transducer for monitoring venous and arterial pressures. Cardiac output determinations were performed by the indicator-dilution method by injecting indocyanine green dye into the superior vena cava or right atrium and sampling from the distal aorta. A pneumotachometer was placed about the animal’s lower chest to monitor respirations. All signals, including a monitoring electrocardiographic lead, were amplified and displayed on a DRI2 Electronics for Medicine recorder. The trauma delivery system consisted of two components l: The first element, a cast aluminum disk, 6.5 cm in diameter and 1.5 cm thick, covered with a thin protective layer of rubber, was centered over the lower sternum of the animal at approximately the fifth intercostal space and secured by adhesive straps. The second element, a Cash-X captive bolt pistol device (supplied by Accles and Shelvoke, Ltd., Talford St. Works, Birmingham, England), was centered perpendicularly at the disk midpoint and fired at end-expiration. The pistol was fixed to a restraining platform to provide even distribution of pressures at the point of impact, to dissipate recoil forces uniformly and to permit remote firing. Bench studies using this system discharged into clay were conducted with a monitoring strain gauge attached to a hollow cylinder interposed between the pistol bolt and the aluminum disk. Impact profiles were developed and demonstrated a spike force of 248 kg occurring maximally at 1 msec and returning to 0 kg by 7 msec. Reproducibility between trials was f0.5 percent. With careful attention to directing the blow to a site on the midsternal axis opposite to the fifth intercostal spaces, a selective injury to the heart was produced with little additional trauma to other organ systems. Injuries to the latter included slight contusions of small segments of overlying lung and occasional rib fractures. Protocol: All experiments were conducted according to the Guide for Laboratory Animal Facilities and Care as outlined by the Institute of Laboratory Animal Resources, National Academy of Sciences. Electrocardiographic and hemodynamic data including values for central venous pressure, systemic arterial pressure, cardiac index (defined as card+ output normalized for animal weight) and peripheral vascular resistance (calculated as the ratio of systemic arterial pressure to cardiac index) were obtained during a resting period in all animals. The protocol was divided into three sections. In the first series of experiments, in nine animals (average weight 13 kg) (Group I), a single standardized blunt chest blow was delivered to the midsternum after control observations. Hemodynamic and electrocardiographic determinations were repeated 0, 10, 30, 60 and 90 minutes after impact and compared with pretrauma values. At the conclusion of the 90 minute trial period, all animals were killed and detailed postmortem ex-
244
February 1975
The American Journal of CARDIOLOGY
aminations of the heart made to determine the extent and location of any gross pathologic injuries to the pericardium or myocardium resulting from the closed chest impact. In two separate experiments, 5 animals in Group II (average weight 15 kg) and 12 in Group III (average weight 17 kg) were pretreated with intravenous infusions of alcohol (0.4 g 200 proof ethanol/kg). Venous blood for assay of alcohol levels was sampled 10 minutes after completion of the infusions. Hemodynamic and electrocardiographic data were obtained at intervals similar to those described for Group I after a 10 minute stabilization period following the infusion of alcohol. No other intervention was introduced to dogs in Group II, but dogs in Group III received a blunt chest blow identical to that administered to animals in Group I. In Group III, either at the end of the 90 minute trial period in surviving animals or after experimental death, postmortem examination of the heart was performed to quantitate the degree of gross anatomic injury. Statistical analysis: Intragroup statistical comparisons of hemodynamic performance were made between pre- and post-impact data in all groups using the paired Student t test; intergroup comparisons of Groups I and III and Groups II and III were performed using the nonpaired Student t test. Statistical significance was defined for probability values of less than 5 percent. Among the electrocardiographic changes observed after trauma were several disorders of rhythm and conduction, including ventricular tachycardia, ventricular fibrillation and complete heart block, either with or without independent ventricular activity. Complete heart block was identified by a total failure of antegrade atrioventricular conduction and consisted of arrhythmias either with atria1 activity exclusively and no ventricular complexes (ventricular arrest) or independent atria1 and ventricular complexes, the latter at less than 60 beats/min and of wide QRS configuration.21
Results Group I (Impact Alone) Hemodynamic data: Eight of nine animals survived closed chest trauma and were studied over the 90 minute observation period (mean survival time 80.3 f 9.6 minutes). One animal died with ventricular fibrillation soon after impact (3.5 minutes). Hemodynamic responses are shown in Figure 1. Cardiac index and mean aortic pressure 10 and 30 minutes after trauma were significantly reduced from pretrauma control values (P
Effects of Alcohol on Cardiovascular Experimental
Nonpenetrating
A. JAMES LIEDTKE, MD WILLIAM E. DeMUTH, MD Hershey,
Pennsylvania
From the Departments of Medicine and Surgery, Divisions of Cardiology and Cardiothoracic Surgery, Pennsylvania State University College of Medicine and The Milton S. Hershey Medical Center, Hershey, Pa. Manuscript accepted June 12, 1974. Address for reprints: A. James Liedtke, MD. Division of Cardiobgy, Department of Medicine, The Mifton S. Hershey Medical Center, Hershey, Pa. 17033.
Performance
After
Chest Trauma
Electrocardiographic and hemodynamic correlates were recorded before and afler a standardized nonpenetrating blow to the chest in 9 anesthetized control dogs (Group I), 5 dogs pretreated with alcohol, 0.4 g/kg intravenously (Group II), and 12 dogs undergolng chest trauma afler alcohol infusions (Group Ill). In animals in Group I, transient major arrhythmias, including complete heart block and ventricular tachycardia, occurred immediately afler impact. One animal died with ventricular fibrillation. In the eight survivors these disturbances were accompanied by acute reductions in aortic pressure and cardiac index; values for both variables gradually increased after restoration of sinus mechanism. Alcohol alone (Group II) produced no significant alterations in either hemodynamic performance or electrical activity, but when combined with nonpenetrating chest injury (Group Ill) it caused a mortality rate of 92 percent, the majority of animals dying with electromechanical dissociation. Mean survival time in Group Ill was 23.1 f 6.5 (standard error of the mean) minutes compared with 60.3 f 9.6 minutes in Group I. At autopsy, minor cardiac lesions of either the pericardium or myocardium were observed in all animals in Groups I and Ill, but none were considered lethal. It is concluded that administration of alcohol, even in small doses, can effect catastrophic reductions in mechanical performance in the presence of otherwise nonfatal cardiac injury secondary to nonpenetrating chest trauma. The clinical implications of this association are discussed.
Previous studies from this laboratory’,2 have demonstrated in a canine model system that nonpenetrating chest trauma causes major changes in left ventricular performance. Traffic accident statistics indicate that such trauma can occur in man, usually after violent contact with the steering column and other fixed automobile accessories in a high speed collision. Such injuries represent a leading cause of death, particularly in younger age groups.3s4 Data from several agencies5 have strongly incriminated excess alcohol intake as a precipitating factor in such fatalities, and alcohol has been shown to have direct pharmacologic effects on the h >art, including both stimulationslo and depression11-20 of m ec h anical performance, inducement of electrical pacemaker asystole and cardiac arrest,2,7,g and a depression in peripheral vasomotor tone, resulting in increased susceptibility to trauma and shock.12JS To date, the specific effects of alcohol on the cardiovascular system after nonpenetrating chest trauma have not been defined. In this study we evaluated and compared several indexes of cardiac performance in response to chest trauma and alcohol, considered both selectively and in combination, in the canine model system previously described.
February 1975
The American Journal of CARDIOLOGY
Volume 35
243
ALCOHOL AND CHEST TRAUMA-LIEDTKE
AND DeMUTH
Methods Twenty-six mongrel dogs, weighing 8.4 to 26.0 kg (average 16.3), were anesthetized with intravenously administered pentobarbital (15 mg/kg body weight) and, after cuffed endotracheal intubation, maintained with methoxyflurane and oxygen under conditions of controlled ventilation. Determinations of arterial pH, and partial pressures of oxygen (PO,) and carbon dioxide (PCOz) and carbon dioxide combining power were obtained throughout the studies to assure adequacy of ventilation and acid-base balance. Animals were secured firmly in the supine position as described previously.1*2 Polyethylene catheters (inner diameter 0.125 inch) were placed in the superior vena cava or right atrium by way of the right jugular vein, and into the aorta by cannulation of a femoral artery. Each catheter was connected to a P23DB Statham pressure transducer for monitoring venous and arterial pressures. Cardiac output determinations were performed by the indicator-dilution method by injecting indocyanine green dye into the superior vena cava or right atrium and sampling from the distal aorta. A pneumotachometer was placed about the animal’s lower chest to monitor respirations. All signals, including a monitoring electrocardiographic lead, were amplified and displayed on a DRI2 Electronics for Medicine recorder. The trauma delivery system consisted of two components l: The first element, a cast aluminum disk, 6.5 cm in diameter and 1.5 cm thick, covered with a thin protective layer of rubber, was centered over the lower sternum of the animal at approximately the fifth intercostal space and secured by adhesive straps. The second element, a Cash-X captive bolt pistol device (supplied by Accles and Shelvoke, Ltd., Talford St. Works, Birmingham, England), was centered perpendicularly at the disk midpoint and fired at end-expiration. The pistol was fixed to a restraining platform to provide even distribution of pressures at the point of impact, to dissipate recoil forces uniformly and to permit remote firing. Bench studies using this system discharged into clay were conducted with a monitoring strain gauge attached to a hollow cylinder interposed between the pistol bolt and the aluminum disk. Impact profiles were developed and demonstrated a spike force of 248 kg occurring maximally at 1 msec and returning to 0 kg by 7 msec. Reproducibility between trials was f0.5 percent. With careful attention to directing the blow to a site on the midsternal axis opposite to the fifth intercostal spaces, a selective injury to the heart was produced with little additional trauma to other organ systems. Injuries to the latter included slight contusions of small segments of overlying lung and occasional rib fractures. Protocol: All experiments were conducted according to the Guide for Laboratory Animal Facilities and Care as outlined by the Institute of Laboratory Animal Resources, National Academy of Sciences. Electrocardiographic and hemodynamic data including values for central venous pressure, systemic arterial pressure, cardiac index (defined as card+ output normalized for animal weight) and peripheral vascular resistance (calculated as the ratio of systemic arterial pressure to cardiac index) were obtained during a resting period in all animals. The protocol was divided into three sections. In the first series of experiments, in nine animals (average weight 13 kg) (Group I), a single standardized blunt chest blow was delivered to the midsternum after control observations. Hemodynamic and electrocardiographic determinations were repeated 0, 10, 30, 60 and 90 minutes after impact and compared with pretrauma values. At the conclusion of the 90 minute trial period, all animals were killed and detailed postmortem ex-
244
February 1975
The American Journal of CARDIOLOGY
aminations of the heart made to determine the extent and location of any gross pathologic injuries to the pericardium or myocardium resulting from the closed chest impact. In two separate experiments, 5 animals in Group II (average weight 15 kg) and 12 in Group III (average weight 17 kg) were pretreated with intravenous infusions of alcohol (0.4 g 200 proof ethanol/kg). Venous blood for assay of alcohol levels was sampled 10 minutes after completion of the infusions. Hemodynamic and electrocardiographic data were obtained at intervals similar to those described for Group I after a 10 minute stabilization period following the infusion of alcohol. No other intervention was introduced to dogs in Group II, but dogs in Group III received a blunt chest blow identical to that administered to animals in Group I. In Group III, either at the end of the 90 minute trial period in surviving animals or after experimental death, postmortem examination of the heart was performed to quantitate the degree of gross anatomic injury. Statistical analysis: Intragroup statistical comparisons of hemodynamic performance were made between pre- and post-impact data in all groups using the paired Student t test; intergroup comparisons of Groups I and III and Groups II and III were performed using the nonpaired Student t test. Statistical significance was defined for probability values of less than 5 percent. Among the electrocardiographic changes observed after trauma were several disorders of rhythm and conduction, including ventricular tachycardia, ventricular fibrillation and complete heart block, either with or without independent ventricular activity. Complete heart block was identified by a total failure of antegrade atrioventricular conduction and consisted of arrhythmias either with atria1 activity exclusively and no ventricular complexes (ventricular arrest) or independent atria1 and ventricular complexes, the latter at less than 60 beats/min and of wide QRS configuration.21
Results Group I (Impact Alone) Hemodynamic data: Eight of nine animals survived closed chest trauma and were studied over the 90 minute observation period (mean survival time 80.3 f 9.6 minutes). One animal died with ventricular fibrillation soon after impact (3.5 minutes). Hemodynamic responses are shown in Figure 1. Cardiac index and mean aortic pressure 10 and 30 minutes after trauma were significantly reduced from pretrauma control values (P
