Irradiation-hyperthermia in canine hemangiopericytomas: large-animal model for therapeutic response.

Results of irradiation-hyperthermia treatment in 11 dogs with naturally occurring hemangiopericytoma were reported. Similarities of canine and human hemangiopericytomas were described. Orthovoltage X-irradiation followed by microwave-induced hyperthermia resulted in a 91% objective response rate. A statistical procedure was given to evaluate quantitatively the clinical behavior of locally invasive, nonmetastatic tumors in dogs that were undergoing therapy for control of local disease. The procedure used a small sample size and demonstrated distribution of the data on a scaled response as well as transformation of the data through classical parametric and nonparametric statistical methods. These statistical methods set confidence limits on the population mean and placed tolerance limits on a population percentage. Application of the statistical methods to human and animal clinical trials was apparent.

High-efficiency endovascular gene delivery via therapeutic ultrasound.

OBJECTIVES: We studied enhancement of local gene delivery to the arterial wall by using an endovascular catheter ultrasound (US). BACKGROUND: Ultrasound exposure is standard for enhancement of in vitro gene delivery. We postulate that in vivo endovascular applications can be safely developed. METHODS: We used a rabbit model of arterial mechanical overdilation injury. After arterial overdilation, US catheters were introduced in bilateral rabbit femoral arteries and perfused with plasmidor adenovirus-expressing blue fluorescent protein (BFP) or phosphate buffered saline. One side received endovascular US (2 MHz, 50 W/cm2, 16 min), and the contralateral artery did not. RESULTS: Relative to controls, US exposure enhanced BFP expression measured via fluorescence 12-fold for plasmid (1,502.1+/-927.3 vs. 18,053.9+/-11,612 microm2, p < 0.05) and 19-fold for adenovirus (877.1+/-577.7 vs. 17,213.15+/-3,892 microm2, p < 0.05) while increasing cell death for the adenovirus group only (26+/-5.78% vs. 13+/-2.55%, p < 0.012). CONCLUSIONS: Endovascular US enhanced vascular gene delivery and increased the efficiency of nonviral platforms to levels previously attained only by adenoviral strategies.

The pumping and left ventricular unloading capabilities of the ventricular synchronous skeletal-muscle ventricle.

The pumping and left ventricular unloading capabilities of the left ventricular, ventricular synchronous skeletal-muscle ventricle were determined in nine anesthetized dogs ranging in weight from 20.7 to 31.8 kg. The ventricular synchronous skeletal-muscle ventricle consists of the left rectus abdominis muscle wrapped around a 4-mil-thick polyethylene pouch (wrapped volume 80 to 100 ml) connected to the left ventricular apex with no valve and to the aorta via a prosthetic heart valve. The rectus muscle is timed to contract tetanically and relax during left ventricular ejection. This arrangement provides a high precontraction pressure for the rectus muscle and a high muscle capillary blood flow during skeletal muscle relaxation. The timing signal for initiation of the train of stimulating pulses (40/sec) was derived from the ventricular electrogram. The delay for the stimulus train determines the preload for the rectus muscle and along with the stimulus train duration determines ventricular synchronous skeletal-muscle ventricle stroke volume, which was measured by electric impedance. With unconditioned rectus muscles (70 to 120 gm) and with a pumping ratio of 1:3, ventricular synchronous skeletal-muscle ventricle stroke volume average 26.1 ml, which provided an average output of 876 ml/min. The normalized ventricular synchronous skeletal-muscle ventricle output was 35.6 ml/min per kilogram of body weight. In a typical resting dog (and man), the normalized cardiac output is 70 ml/min per kilogram. Therefore the ventricular synchronous skeletal-muscle ventricle is capable of pumping 52% of the cardiac output (with a pumping ratio of 1:3). The optimum train delay from the apex of the ventricular electrogram ranged from 10 to 100 msec. The left ventricular ejection period averaged 309 msec, and this determines the time available for the rectus muscle to contract and relax. Evidence for unloading the left ventricle is shown by the reduced left ventricular diastolic pressure and stroke volume for the postassisted beats.

Output power and metabolic input power of skeletal muscle contracting linearly to compress a pouch in a mock circulatory system.

Output power and metabolic input power values were determined for unconditioned canine latissimus dorsi (two), gastrocnemius (seven), and triceps (three) muscles contracting linearly to cause compression of a doubly valved pouch in a hydraulic model of the circulation. The motor nerves to the muscles were stimulated tetanically with 450 msec trains of 0.1 msec pulses having a frequency of 50/sec. The muscles were contracted 10, 20, 30, and 40 times per minute and pouch output in milliliters per minute was measured directly for each muscle at each contraction (train) rate. The output power in milliwatts was determined by two methods: (1) by using the pouch output and the pressure rise imparted to the stroke volume (average power) and (2) by using the pressure-volume loop. Metabolic input power in milliwatts was determined from the oxygen consumption in milliliters per minute of the working muscle. It was found that as the pouch output was increased, the pouch output power and the metabolic input power both increased. The average power output was slightly less than that computed from the pressure-volume loop. The mean output power values, when pumping at L liters per minute, were 0.62 L (average) and 0.75 L mW/gm (pressure-volume loop) for the latissimus dorsi muscles; 0.83 L (average) and 1.16 L mW/gm (pressure-volume loop) for the gastrocnemius muscles; and 0.55 L (average) and 0.66 L mW/gm (pressure-volume loop) for the triceps muscles. The percent efficiency of energy conversion ranged from 9.2% to 17.8% for the latissimus dorsi muscles, from 5.1% to 19.5% for the gastrocnemius muscles, and from 10.5% to 27.3% for the triceps muscles. However, it should not be concluded that one muscle type is better than another on the basis of percent efficiency because efficiency does not take endurance into account. An important observation in this study relates to the large output obtained with the three linearly contracting muscle types. All were capable of pumping in excess of 1.5 L/min. A second observation relates to the absence of fatigue, although determination of endurance was not an objective in these studies.

The comparative pathology of open chest vs. mechanical closed chest cardiopulmonary resuscitation in dogs.

We compared the pathologic changes following open-chest cardiopulmonary resuscitation (OCCPR) vs. closed chest cardiopulmonary resuscitation (CCCPR) in 28 healthy mongrel dogs subjected to experimentally induced ventricular fibrillation (VF). VF was induced in 29 dogs. No treatment was given for 3 min, then mechanical CCCPR was given for the next 12 min. External defibrillation (80 joules) was then attempted twice. One dog was resuscitated. The remaining 28 dogs were divided into 2 groups of 14 each. Group A received continued CCCPR and group B received OCCPR. All dogs received advanced cardiac life support and were followed until resuscitated or dead. All dogs were autopsied and gross pathology scores and histopathology scores were determined for each animal, and for each of 19 separate tissues within each animal. The mean gross pathology scores for the following tissues were significantly greater for dogs that received OCCPR vs. those that received CCCPR: skin (3.4 vs. 1.2; P less than 0.001), subcutaneous tissue (3.7 vs. 0.6; P less than 0.001), chest wall muscle (3.7 vs. 0.5; P less than 0.001), and pleura (1.9 vs. 0.1; P less than 0.001). The mean total gross pathology score was also greater in dogs that received OCCPR vs. those that received CCCPR (17.2 vs. 7.7; P less than 0.001). The mean histopathology scores for the following tissues were significantly greater for dogs that received OCCPR vs. those that received CCCPR: skin (2.5 vs. 0.0; P less than 0.001), subcutaneous tissue (2.2 vs. 0.1; P less than 0.001), muscle (2.3 vs. 0.1; P less than 0.001), pleura (1.6 vs. 0.0; P less than 0.001), pericardium (1.4 vs. 0.2; P less than 0.01), epicardium (2.5 vs. 0.2; P less than 0.001), myocardium (2.5 vs. 0.3; P less than 0.001), and endocardium (1.9 vs. 0.5; P less than 0.01). The mean total histopathology score was also greater in dogs that received OCCPR vs. those that received CCCPR (20.1 vs. 7.4; P less than 0.001). The histopathology score for brain tissue was greater for the CCCPR group than for the OCCPR group (1.9 vs. 0.4; P less than 0.05). This study showed that OCCPR in dogs following VF caused more severe pathologic changes than CCCPR. These changes were attributed to thoracotomy-induced chest wall injury and to internal defibrillation induced myocardial injury. However, OCCPR caused less severe microscopic brain lesions than CCCPR.

Depletion of myocardial adenosine triphosphate during prolonged untreated ventricular fibrillation: effect on defibrillation success.

We studied left ventricular endomyocardial adenosine triphosphate levels in 13 large mongrel dogs before and during ventricular fibrillation induced cardiac arrest to assess whether myocardial adenosine triphosphate content could predict successful cardiopulmonary resuscitation. Endomyocardial biopsies were performed during sinus rhythm (control), after 15 min of ventricular fibrillation or 10 min of ventricular fibrillation and 5 min of open chest cardiopulmonary resuscitation, after 20 min of ventricular fibrillation and 10 min of open chest cardiopulmonary resuscitation and after 40 min ventricular fibrillation and 15-20 min open chest cardiopulmonary resuscitation. Myocardial adenosine triphosphate was measured utilizing a bioluminescence method adapted for use with endomyocardial biopsies and normalized to protein content. Left ventricular endomyocardial adenosine triphosphate content fell significantly over time from a control level of 8.88 +/- 0.9 micrograms/mg protein to 5.73 +/- 0.5 micrograms/mg protein at 15 min of cardiac arrest, to 3.4 +/- 0.4 micrograms/mg protein after 30 min of cardiac arrest and to 1.98 +/- 0.3 micrograms/mg protein after 60 min of cardiac arrest (P less than 0.001). Adenosine triphosphate levels were significantly different between animals that received 10 min of ventricular fibrillation and successful open chest cardiopulmonary resuscitation and those that received 40 min of ventricular fibrillation and unsuccessful open chest cardiopulmonary resuscitation (4.35 +/- 0.48 vs. 2.11 +/- 0.43 micrograms/mg protein; P less than 0.025).(ABSTRACT TRUNCATED AT 250 WORDS)

Use of impedance ratio for the continuous measurement of stroke volume of a valveless pouch used as a cardiac-assist device.

A technique is described for measuring the volume of a valveless compressible plastic pouch and its volume change when used as a cardiac-assist device. The method employs measuring the pouch impedance at high frequency with sleeve electrodes at both ends of the pouch. The use of an adequately high frequency eliminates the electrode impedance and the impedance measured is that of the resistance of the electrolyte in the pouch. By equating the compressible pouch to two truncated cones with their bases adjacent, an equation is derived that relates pouch impedance to volume. It is shown that by plotting the stroke volume ejected (delta V) versus the ratio of systolic (RS) to diastolic (Rd) impedance, the resulting relationship is independent of the resistivity of the fluid in the pouch. Validation tests were made with a 100 mL pouch filled with solutions having resistivities of 60, 102, 145, and 192 omega-cm. The method described herein permits calibration of the volume change of a valveless pouch used as a circulatory-assist device and in use the calibration will not be affected by a change in packed-cell volume which changes resistivity.

Histology after dural grafting with small intestinal submucosa.

BACKGROUND: The search for the ideal dural substitute continues, inasmuch as available materials have significant limitations. Xenogeneic porcine small intestinal submucosa (SIS) has been successfully used as a soft tissue graft in several body organ systems, and it was logical to evaluate its use as a dural replacement. METHODS: Twenty rats underwent bihemispheric craniectomy with dural resection. SIS onlay grafting on one side was performed. Histologic assessment was obtained at 7 and 28 days after dural grafting and included descriptive evaluation and quantitative scoring of graft-site thickness, vascularity, and cellular density. The total scores for the respective groups were compared using the Student's t test, significance being accepted for a p value < 0.05. RESULTS: Histologic evaluation showed graft infiltration by spindle-shaped mononuclear cells, deposition of connective tissue, and neovascularity. This pattern is consistent with the previously described incorporation and remodeling of the SIS graft at other sites. A significant difference between the histologic scores of the SIS graft site and control site was found at 7 days (3.4 +/- 0.8 versus 0.1 +/- 0.1) and at 28 days (4.6 +/- 1.1 versus 2.2 +/- 0.5). No evidence of adverse effect on the underlying cortex was observed. CONCLUSIONS: The results of this preliminary study utilizing porcine SIS as a dural substitute are promising and therefore justify further chronic studies.

Porcine small intestinal submucosa as a dural substitute.

BACKGROUND: The continuing search for the ideal dural substitute is currently directed toward collagen preparations. Xenogeneic porcine small intestinal submucosa (SIS), a naturally occurring extracellular matrix rich in collagen, has been successfully used as a soft tissue graft in several body organ systems, including preliminary studies as a dural substitute in the rat. METHODS: Eight dogs underwent temporoparietal craniotomy and dural resection with replacement by SIS. Five dogs had contralateral procedures without SIS grafting. Three dogs had contralateral SIS grafts placed 2 months after the initial procedure. Histologic assessment was obtained at 7, 30, 60, 90, and 120 days. Cerebrospinal fluid (CSF) cytological examination and routine serum chemistry preceded sacrifice. RESULTS: Histologic evaluation showed initial graft infiltration by mononuclear round cells, spindle-shaped cells within an eosinophilic staining extracellular matrix, and neovascularity. Complete resorption of the graft was evident by 60 days. This pattern is consistent with the previously described incorporation and remodeling of the SIS graft at other sites. CSF cytology and routine serum chemistry at the time of sacrifice were normal. Response to repeat grafting was identical to that of initial exposure. There was no clinical or histologic evidence of sensitization or graft rejection. No evidence of adverse effect on the underlying cerebral cortex was observed. CONCLUSIONS: Porcine small intestinal submucosa demonstrates a favorable biologic response as a dural substitute in the canine model. It is a promising biomaterial for dural replacement.

The effect of skeletal muscle ventricle pouch pressure on muscle blood flow.

Skeletal muscle powered assist ventricles (SMV) are being investigated in animal studies as a treatment for heart failure. Muscle fatigue is almost always dependent upon muscle capillary blood flow. This study examined the relationship between SMV intrapouch pressure and blood flow to the circumferential muscle in a working SMV with a mock circulation. The unconditioned rectus abdominis muscle was used to create an in situ SMV in five dogs. Muscle blood flow was measured by both the radioactive microsphere and the electromagnetic flow probe method as the pouch pressure was varied between 10 and 70 mmHg and as the SMV was stimulated to contract at a rate of 20 min-1. The correlation coefficient for the two methods was 0.908. At pouch pressures of 10, 40, and 70 mmHg, the respective blood flow values were 22.60 +/- 2.50 (1 SEM), 12.20 +/- 2.10, and 4.40 +/- 0.74 ml min-1 (p less than 0.05). When they were corrected for muscle weight, the mean blood flow values at these same pouch pressures were 0.28 +/- 0.03, 0.15 +/- 0.03, and 0.05 +/- 0.01 ml min-1 g-1, respectively (p less than 0.05). SMV output was measured for each pouch pressure that was tested. Pouch output, expressed as ml min-1, was 458 +/- 20 (1 SEM) at an SMV diastolic pouch pressure of 10 mmHg, 309 +/- 22 at a pouch pressure of 40 mmHg, and 103 +/- 6 at a pouch pressure of 70 mmHg.(ABSTRACT TRUNCATED AT 250 WORDS)

Use of electrical impedance for continuous measurement of stroke volume of a skeletal muscle-powered cardiac assist device.

This study describes the use of electrical impedance Z to continuously measure the stroke volume SV of a skeletal muscle-powered ventricle (SMV). An SMV was constructed surgically in four anaesthetised dogs. The rectus abdominis (two dogs) or latissimus dorsi (two dogs) muscle was wrapped around a compressible pouch, the ends of which were connected to a saline-filled (0.9 per cent) mock circulation. The motor nerves to the muscle were stimulated to produce tetanic contractions at a rate of 10 min-1. Z was measured between brass sleeve electrodes within the end conduits of the pouch. To derive a simple expression relating pouch volume V to Z, the pouch was represented as two truncated cones with their bases joined. For V ranging from 53 to 103 ml, the relationship between Z and 1/square root of V was nearly linear; i.e. Z = m(1/square root of V) + b. Impedance-derived stroke volume SV (delta Z) was calculated using this linear approximation and the impedance measured just before and after muscle contraction. The stroke volume SV (EM) ejected by the pouch during muscle contraction was measured with an electromagnetic flowmeter. The linear regression coefficients ranged from 0.99 to 2.55; the correlation coefficients ranged from 0.90 to 0.98. In general, SV(delta Z) tracked SV(EM) very well, although SV(delta Z) tended to overestimate SV(EM).

Cardiac assistance with electrically stimulated skeletal muscle.

This study examined the ability of a skeletal muscle-powered assist ventricle (SMV) to augment cardiac output in ten dogs with pharmacologically induced heart failure under acute conditions. An SMV was surgically constructed in each dog by wrapping the untrained rectus abdominis muscle around a compressible pouch that was inserted into a left ventricular apex-to-aortic vascular conduit. The multiple motor nerves to the rectus muscle were then stimulated during ventricular diastole at a rate which equalled a ratio of 1:2, 1:3, or 1:4 with the natural ventricular beat. There was an increased cardiac output during SMV assistance compared with preassistance values in all ten dogs at each stimulation ratio with a mean increase of 46 +/- 4 per cent with a ratio of 1:2, 25 +/- 4 per cent with a ratio of 1:3, and 31 +/- 7 per cent with a ratio of 1:4 (p less than 0.01 for all values). The diastolic blood pressure and mean blood pressure were both increased (p less than 0.01 and p less than 0.05, respectively) during SMV stimulation at ratios of 1:2 and 1:3, but not 1:4. We have shown that untrained rectus abdominis muscle, when used as the power supply for a SMV in an apico-aortic conduit, can temporarily augment cardiac output in dogs with pharmacologically induced heart failure.

Indirect auscultatory systolic and diastolic pressures in the anesthetized dog.

The auscultatory method was used to obtain indirect systolic and diastolic pressures in 13 dogs anesthetized with either halothane or sodium pentobarbital (30 mg/kg of body weight). Korotkoff sounds were obtained, using a 1-cm (diameter) piezoelectric element cemented to the inner surface of a pediatric cuff (width 5.5 cm) which was placed on a shaved thoracic limb (membrum thoracicum). The signal from the piezoelement was amplified by a differential amplifier (30 to 200 Hz) and a commercially available audio amplifier. Indirect pressure (I) was compared with direct pressure (D) in the brachial, femoral, or carotid artery. The linear regression lines and correlation coefficients (r) for the data were as follows: systolic, I = 0.94 (D) + 1.1, r = 0.98; diastolic, I = 0.99 (D) + 3.2, r = 0.99. The quality of the Korotkoff sounds and the accuracy of the determinations were best in the halothane-anesthetized dogs. These results indicate that indirect auscultatory systolic and diastolic pressures are in excellent agreement with the directly measured pressures.

Nonpharmacologic circulatory support in the brain-dead animal.

A nonpharmacologic technique for providing an artificial peripheral resistance enabled the canine heart to pump blood for 12 hours in a brain-dead (spinal) animal model. The artificial peripheral resistance was provided by binding the body with elastic bandage. The only other support provided was artificial respiration. Following the 12-hour preservation period, the hearts were challenged to pump by the intravenous infusion of saline. Aortic pressure, cardiac output (CO), oxygen uptake, body temperature, arterial Na+, K+, pH, and HCO3-, and transchest ECG were monitored in all five animals studied during the control and 12-hour preservation periods. Mean blood pressure fell to 50-60 mmHg following cervical cord transection, rising to above 100 mmHg when the body was bound with elastic bandage that restored the peripheral resistance. During the 12-hour preservation period the average mean blood pressure fell from 118 to 60 mmHg, at which point the average normalized CO was 34 mL/min/kg. Following the saline challenge, the average CO increased to 1.89 times the value at the end of the preservation period, representing an average normalized value of 64.3 mL/min/kg (a typical value for the normal resting dog is 70 mL/min/kg). Body temperature decreased slightly in four animals and increased slightly in one. Na+ was virtually unchanged throughout the control and preservation periods, but K+ increased slightly in all animals, exceeding 5 mEq/L in one animal after 8.5 hours and in another after 10 hours. HCO3- was almost constant in all animals, as was pH. However, the pH was elevated during the preservation period due to slight overventilation to assure a high oxygen saturation.(ABSTRACT TRUNCATED AT 250 WORDS)

A selective, non-ischemic, non-pharmacological left ventricular failure animal model.

Selective left ventricular failure was induced in 13 acute anesthetized, closed chest dogs ranging in weight from 18-26 kg. Failure was induced by passing a single, high intensity pulse of current from a defibrillator connected to a left ventricular catheter electrode and a left chest electrode. The intensity of the myocardial damaging shock was related to the predicted current required for transventricular defibrillation, based on heart weight. Thermodilution cardiac output, left ventricular pressure, impedance stroke volume, the cardiac electrogram, and lead II ECG were recorded, along with the pressure impedance (volume) loop, which is a measure of stroke work. It was found that the cardiac output decreased with increasing current intensity. Immediately following the high current shock, cardiac output, and stroke work decreased. In some animals, with a moderate intensity shock, there was a transient increase in cardiac output, followed by a decrease. In the five animals that were monitored continuously for 4 hours, the average percent reduction in cardiac output at this time was 42.5% for an average current overdose ratio of 5.39. The energy setting on the defibrillator to obtain this range of reduction in cardiac output was 175-350 joules. The method described herein is easily applied to the closed chest animal and will allow evaluation of the pumping capabilities of cardiac augmentation techniques, such as dynamic cardio-myoplasty and the skeletal muscle ventricle.

Pumping capabilities of the latissimus dorsi and rectus abdominis muscles wrapped around a valved pouch in a mock circulatory system.

The pumping capabilities of nine unconditioned canine rectus abdominus muscles (93-163 gm) and six latissimus dorsi muscles (99-146 gm) were measured. The muscles were wrapped around a 100 ml ellipsoidal pouch in a mock circulatory system in which the afterload was 100 mmHg. Pouch diastolic pressure was kept low by an electrically controlled inlet valve to maximize muscle capillary blood flow. Immediately before tetanic contraction of the pouch-encircling muscle, the inlet valve opened for 450 msec to increase pouch pressure to 100 mmHg, thereby providing a high preload and ensuring a forceful muscle contraction. The motor nerves to the muscles were stimulated with 450 msec trains of 0.1 msec stimuli, using a frequency of 40/sec. The train rates (muscle contractions/min) were 10-50/min. In this circulatory model it was found that the maximum output for both muscle types occurred between 20 and 40 contractions/min. It was also found that for both muscle types, the maximum output (L/min) was dependent upon muscle weight. The data revealed that an output of 4 ml/min was obtained per gram of muscle. The power (mW/gm) developed was related to the output (L) in L/min. For the rectus muscle W = 0.47L, and for the latissimus muscle W = 0.41L mW/gm. Pumping periods lasted approximately 4 hours, with no evidence of fatigue. When viewed as a potential cardiac assist device, the muscles were able to provide a flow equivalent to approximately 25% of the cardiac output. However, it is important to note that the pumping capability is directly related to muscle weight, indicating that a higher output can be achieved with a larger muscle.

Comparison of canine skeletal muscle power from twitches and tetanic contractions in untrained muscle: a preliminary report.

Power output and blood flow were determined in dogs for four muscles (gastrocnemius, latissimus dorsi, rectus abdominis, and triceps) to determine effects of choice of muscle, tetany or twitch rates, force loading of the muscle, and blood flow on muscle power output. Total power for a 20-Kg dog was greatest for triceps at 0.77 watts (W) and least for rectus at 0.22 W; power per gram was greatest for gastrocnemius at 5.77 mW/g. Muscle perfusion of latissimus and rectus is greatly decreased by overstretching of the muscle. Overstretching also produces severe, persistent, power loss in latissimus and rectus muscles. Gastrocnemius and triceps tolerate stretching much better. We conclude that power can be improved without causing muscle fatigue by choice of muscle, choice of electrical stimulation parameters, linear geometry for contraction of the muscle, and matching the force load to each individual muscle.

Stroke volume with dynamic cardiomyoplasty during ventricular fibrillation in the acute dog.

The objective of this study was to determine the pumping capability of dynamic cardiomyoplasty during induced ventricular fibrillation. In this acute study of 6 dogs, the pumping capability of the unconditioned left latissimus dorsi (LD) muscle (141 to 292 gm), wrapped around both ventricles, was investigated during induced ventricular fibrillation. Left-ventricular and femoral artery pressure, the ECG and aortic root flow velocity were monitored. Prior to inducing ventricular fibrillation, the ability of the unconditioned LD muscle to augment stroke volume (SV), was quantified as the area under the aortic flow-velocity record. The ventricles were then fibrillated and, after 10 sec, rhythmic 250 msec trains (1/sec) of stimuli (40/sec) were delivered to the thoracodorsal nerve to contract the LD muscle tetanically. In no case could dynamic cardiomyoplasty produce the same SV as when the ventricles were beating normally. In one animal, the SV attained two percent of the normal SV by 5 contractions; in another, the SV reached one percent by 25 contractions. In the remaining animals, the SV varied around 20% of the prefibrillation SV. By 90 contractions, the stroke volume was 10% of the prefibrillation value. The progressive decrease in SV was likely a consequence of LD muscle ischemia and fatigue, since the latissimus dorsi muscle provided low blood flow during the period of fibrillation.

Cardiac output versus pacing rate at rest and with exercise in dogs with AV block.

To achieve maximum benefit from exercise (rate)-responsive pacing in subjects with sinus node dysfunction and AV block, it is necessary to determine the pacing rate (HR) which produces maximum cardiac output (CO) under specified exercise conditions. However, the CO-HR relationship for exercise has not been systematically investigated. To permit determination of the optimum HR, CO was measured at rest and with exercise for different pacing rates. Seven dogs with complete AV block and permanently implanted ventricular pacemakers were exercised on a treadmill for 5 min at each of four pacing rates (55, 76, 101, 116/min) and at two constant exercise levels (225 and 560 kg.m/min). CO was determined by impedance cardiography during the resting state preceding exercise and during a brief period (10-20 s) immediately after exercise, and was expressed as a percent of the CO determined at rest with HR = 55/min. A three-phase pattern of CO versus HR appears to exist for exercise as for rest. For exercise, starting from a low HR, CO increases markedly; a "plateau" is reached during which moderate increase in CO is achieved by increasing HR. At very rapid pacing rates, CO may actually decrease with further increase in HR. The results of this study suggest that a subject-specific optimum HR exists for each constant exercise level. Moreover, the methodology employed in the study is applicable to the identification of optimum HR for any exercise (rate)-responsive pacemaker.