Efficacy of nitroprusside therapy in postcardiotomy low-output syndrome necessitating intra-aortic balloon counterpulsation.

Serial hemodynamic measurements were obtained before, during, and after nitroprusside therapy over a 24 hour period in 19 patients requiring intra-aortic balloon pumping (IABP) for successful weaning from cardiopulmonary bypass. Nitroprusside, administered in doses ranging from 0.5 to 5 micrograms/kg/min, effected significant reductions in mean aortic pressure and systemic vascular resistance within 20 to 30 minutes. Mean aortic pressure decreased from 108 +/- 22 mm Hg to 85 +/- 27 mm Hg (p less than 0.005). Systemic vascular resistance decreased from 2,705 +/- 1,072 to 1,942 +/- 823 dynes sec cm-5 (p less than 0.005). 2n response to nitroprusside-induced decreases in left venticular afterload, cardiac indes increased from 1.83 +/- 0.58 to 2.04 +/- 0.54 L/min/m2 (p less than 0.025). Pulmonary capillary wedge pressure (PCW), right atrial pressure, right and left ventricular minute work indices, and the rate-pressure products did not change, indicating that nitroprusside administration during IABP further increased cardiac output without increasing ventricular filling pressure, ventricular work, or indices of myocardial oxygen consumption. The data suggest that nitroprusside, in conjunction with volume loading to optimal preload levels (PCW = 15 to 18 mm Hg), augments ventricular performance in postcardiotomy low-output syndrome by lowering impedance to left ventricular ejection through a direct dilator effect on vascular smooth muscle, without a direct effect on cardiac muscle. Thus it is a valuable pharmacologic adjunct during mechanical (IABP) support of the failing circulation.

Combined use of dopamine and nitroprusside therapy in conjunction with intra-aortic balloon pumping for the treatment of postcardiotomy low-output syndrome.

Intra-aortic balloon pumping (IABP) has been utilized in our institution in over 600 patients for the treatment of postcardiotomy low-output syndrome, with a 59% survival rate. Volume loading and pharmacologic treatment have played integral roles in the overall treatment of this syndrome. This investigation documents the hemodynamic effectivenss of combined nitroprusside/dopamine therapy in patients who required IABP for weaning from cardiopulmonary bypass. Serial hemodynamic measurements were made before and during infusion of nitroprusside (0.5 to 5.0 microgram/kg/min) and after combined nitroprusside/dopamine (7.5 micrograms/kg/min) therapy in 10 patients during IABP. Prior to pharmacologic therapy, cardiac index was 1.6 +/- 0.4 L/min/m2 and systemic vascular resistance (SVR) was 2,774 +/- 932 dynes sec cm-5. After nitroprusside infusion, cardiac index increased to 1.8 +/- 0.5 L/min/m2 (NS) and SVR decreased to 1,957 +/- 791 dynes sec cm-5 (p less than 0.01). The simultaneous infusion of nitroprusside and dopamine resulted in further augmentation of cardiac index to 2.5 +/- 0.5 L/min/m2 (p less than 0.01) and an additional reduction of SVR to 1,439 +/- 358 dynes sec cm-5 (p less than 0.02). In addition, pressure-rate-product, an index of myocardial oxygen demand, was decreased by nitroprusside (p less than 0.02) but was not significantly altered by both agents. This study provides a rationale for the combined use of nitroprusside/dopamine in postcardiotomy low-output syndrome necessitating IABP when SVR is greater than 2,000 dynes sec cm-5 and cardiac index is less than 2.0 L/min/m2.

Development and evaluation of electrically actuated abdominal left ventricular assist systems for long-term use.

A long-term, totally implantable, electrically actuated, abdominally positioned left ventricular assist system (ALVAS) is being developed, characterized in vitro, and evaluated in vivo for utilization in patients with end-stage cardiac failure refractory to conventional therapeutic techniques. The first two major subsystems of the ALVAS (the pusher-plate blood pump and electrical-mechanical energy converters) have been integrated and are undergoing in vitro characterization and long-term in vivo evaluations in calves. Duration of these studies has exceeded 6 months. System performance in terms of hemodynamic effectiveness, mechanical reliability, and biocompatibility has been excellent and no untoward effects have been observed. Long-term effectiveness of the ALVAS remains to be established in continuing experiments, with a 2 year period of clinical use as an ultimate goal.

Prognostic indices for survival during postcardiotomy intra-aortic balloon pumping. Methods of scoring and classification, with implications for left ventricular assist device utilization.

To define more clearly a salvageable patient for possible utilization of a left ventricular assist device prior to multiple organ failure and irretrievability during postcardiotomy intra-aortic balloon pumping (IABP), we made prospective and retrospective analyses to determine prognostic indices for survival. Serial left ventricular function curves (IABP on-off), scoring methods, hemodynamic and renal function tracking trajectories, survival versus nonsurvival data envelopes, and classification methods were developed and used. All patients requiring postcardiotomy IABP support who were in Class A survived; 80 percent of the patients in Class B survived. All patients who remained in Class C for 12 hours or more following operation with IABP support died. These preliminary analyses suggest that the postcardiotomy IABP-supported patient with a score of less than 6 who remains in Class C for 12 hours or more is at the highest possible risk and is a probably candidate for more effective support with a left ventricular assist device.

An intracorporeal (abdominal) left ventricular assist device. Initial clinical trials.

We have initiated clinical trials with an intracorporeal (abdominal) partial artificial heart and ten preterminal postcardiotomy patients have been studied. During profound left ventricular failure, the device captures the entire cardiac output from the apex of the left ventricle at low pressures (20 to 40 mm Hg) and ejects (at 80 to 150 mm Hg) into the infrarenal abdominal aorta; the biological aortic valve opens only intermittently and the entire systemic circulation is pump generated. The device is six to ten times more effective than intra-aortic balloon pumping in man and has maintained systemic perfusion during clinical asystole and ventricular fibrillation. We have documented that the profoundly depressed postcardiotomy left ventricle, initially incapable of ejection, can recover during total left ventricular unloading with the abdominal left ventricular assist device support over a seven-day period.

Myocardium-sparing cannulation technique for left ventricular assist device support.

The left atrium and the left ventricular apex are the most commonly used sites of inflow cannulation for postcardiotomy left ventricular support. A new cannulation technique that requires only an ascending aortotomy is introduced. This procedure can be undertaken with equipment present in any cardiac operating room and may prove to cause fewer complications than conventional cannulation techniques.

Effects of an abdominal left ventricular assist device on myocardial oxygen supply/demand ratios in normally perfused and ischemic bovine myocardium.

The effects of an abdominal left ventricular assist device (ALVAD) on subendocardial oxygen supply/demand ratios as reflected by diastolic pressure-time index/tension-time index (DPTI/TTI) were investigated in calves. Control DPTI/TTI ratios were 1.09 plus or minus 0.12 (mean plus or minus SD). With ALVAD actuation the ratios increased to 5.73 plus or minus 3.2. Following circumflex coronary artery occlusion, control ratios decreased to 0.04 plus or minus 0.05 in the ischemic area and 0.97 plus or minus 0.20 in the nonischemic areas. With ALVAD actuation in the presence of circumflex occlusion, the depressed ratios were increased to 1.37 plus or minus 0.39 in the ischemic zone and 9.71 plus or minus 2.5 in the nonoccluded segments. Subendocardial oxygen supply/demand ratios were significantly improved by ALVAD assistance following induced subendocardial ischemia.

An abdominal left ventricular assist device: preclinical studies.

An abdominally positioned left ventricular assist device (ALVAD) has been evaluated in our most recent series of 25 calves weighing 99 plus or minus 12 kg. The ALVAD is a pneumatically actuated bladder pump, positioned subdiaphragmatically and connected between the left ventricular apex and the infrarenal abdominal aorta. The mean survival time in the calves was 41 days and the longest 65 days. The major effects of the pump are reduction of all indices of left ventricular work and increases in systemic perfusion. In the awake, unanesthetized calf, left ventricular pressure, dP/dt, and stroke work were decreased while peak aortic pressure, stroke volume, and cardiac output increased. These effects were corroborated at cardiac catheterization two to four weeks postoperatively; left ventriculograms also showed increases in ejection fraction. These data demonstrate the ALVAD's effectiveness in assuming left ventricular function and support over extended periods. The device has been developed for short-term postoperative clinical use in patients with reversible left ventricular failure.

Production of controlled reversible left ventricular failure in calves using intracoronary lidocaine hydrochloride: a useful method of evaluating left ventricular assist devices.

The experimental production of stable, controlled, short-term left ventricular failure is valuable in the evaluation of implantable circulatory support systems. Acute or chronic left ventricular failure produced by occlusion or embolization of coronary arteries results in muscle dysfunction and degrees of failure that may be difficult to control. The effects of varying amounts of intracoronary lidocaine were studied during short- and long-term evaluations of intracorporeal left ventricular assist pumping. In 8 Hereford calves the left main coronary artery was cannulated with an intracoronary catheter in open and closed chest preparations. Dose-related negative inotropic effects were noted when lidocaine was injected at individual doses of 50, 75, and 100 mg. Following 100 mg doses, mean aortic pressure, cardiac output, and maximum rate of rise of left ventricular pressure decreased; left ventricular end-diastolic pressure increased fourfold. Similar effects were noted with short continuous infusions of lidocaine. The initial responses to injection or continuous infusions, if effective, were noted within 40 to 60 seconds. Several episodes of failure could be produced with either method following recovery periods of 10 to 15 minutes. In all instances, actuation of a left ventricular assist device immediately reversed the hemodynamic effects of the pharmacologically induced failure.

Minimally invasive access of the normal pericardium: initial clinical experience with a novel device.

The pericardial space is being investigated as a reservoir for local drug delivery to the heart and coronary arteries. Intrapericardial drug delivery is currently limited because the pericardial space is normally small and difficult to access by standard pericardiocentesis without invasive surgery or risk of cardiac injury. Clinical trials are being conducted to evaluate a novel, minimally invasive, pericardial access device (PerDUCER, Comedicus Inc., Columbia Heights, Minn.). As of October 26, 1998, 12 clinical trials have been completed on patients undergoing cardiac surgical procedures. In all patients, a stab incision was made 1" subxiphoid and a 17G angled cannula, with preloaded guidewire, was advanced into the mediastinal space. After cannula removal, a 19F sheath/dilator was inserted over the wire. In eight patients, a median sternotomy was performed and the position of the sheath over the anterior pericardium (PC) was visually verified. Four patients underwent a closed-chest, fluoroscopy-assisted procedure. In all patients, the PerDUCER was inserted into the chest, via the sheath, and positioned over the PC. The PC was captured by suction and a bleb was formed within a side-hole on the PerDUCER tip. A sheathed needle was advanced, puncturing the isolated bleb of PC. A guidewire was advanced through the needle into the pericardial space and the PerDUCER was removed. Guidewire insertion was successful in 10 patients (7 on first attempt, 3 on second) without adverse hemodynamic effects or arrhythmia. Other than the guidewire insertion site, there was no evidence of injury to the PC or the heart. These initial clinical trials suggest that the PerDUCER may provide safe, rapid and effective percutaneous insertion of a guidewire into the normal pericardial space.

Evolution of the Texas Heart Institute Distant Organ Procurement Program.

Between August and December 1983, the Texas Heart Institute Transplantation Service performed 10 cardiac transplants. All hearts were removed at outside hospitals and transported to the Heart Institute. Adequate return of cardiac function occurred in all groups after ischemic times of 58.5 minutes for hearts procured within Houston (range, 56-62 minutes) and 152 minutes for those procured in other cities (range, 130-179 minutes). Eight of the transplant patients are alive and well following operation. Distal procurement has more than doubled the number of suitable organs, and offers considerable potential for expansion of the transplant program.

Localized administration of sodium nitroprusside enhances its protection against platelet aggregation in stenosed and injured coronary arteries.

Sodium nitroprusside, a potent vasodilator, was evaluated for its effect on platelet aggregation in stenosed and endothelium-injured coronary arteries in a canine model. Twenty-five anesthetized dogs were studied; coronary blood flow velocity was continuously monitored. Recurrent intracoronary platelet aggregation and dislodgment (indicated by cyclic variations in coronary blood flow) were induced by mechanically injuring and stenosing the left anterior descending coronary artery. Sodium nitroprusside was administered either intrapericardially or intravenously 30 min after cyclic flow variations were established. Intrapericardial administration of saline (control) did not affect cyclic flow variations in any of 6 tested dogs. Sodium nitroprusside abolished cyclic flow variations in all 7 dogs (100%) when given intrapericardially and in 5 to 7 dogs (71%) when given intravenously (compared to intrapericardial salines, p < 0.01). A smaller dose of sodium nitroprusside was required to abolish cyclic flow variations when given intrapericardially than when given intravenously (1.6 +/- 0.5 micrograms.kg-1.min-1 vs 4.8 +/- 0.8 micrograms.kg-1.min-1, p < 0.01). The mean aortic pressure was reduced by 10 to 20 mmHg after intrapericardial sodium nitroprusside administration and by 30 to 40 mmHg after intravenous sodium nitroprusside administration. To investigate the mechanism of protection by sodium nitroprusside, NG-monomethyl-L-arginine, an inhibitor of nitric oxide synthetase, was used to induce cyclic flow variations in mildly injured and stenosed left anterior descending coronary arteries in 5 dogs. Intrapericardial sodium nitroprusside abolished the cyclic flow variations in all 5 dogs. Then oxyhemoglobin, an inhibitor of nitric oxide, was administered into the left anterior descending coronary arteries of these dogs, and it restored the sodium nitroprusside-abolished cyclic flow variations in all 5 dogs. Thus, sodium nitroprusside protects against platelet aggregation and cyclic flow variations in stenosed and endothelium-injured canine coronary arteries, probably by the action of nitric oxide, and it is more effective and hemodynamically safer when administered intrapericardially than when administered intravenously.

Calcification in chronically-implanted blood pumps: experimental results and review of the literature.

Blood compatibility is a major objective in the development of long-term, implantable circulatory assist (left ventricular assist devices) and replacement (total artificial heart) devices. An important problem in experimental studies in animals has been the propensity for calcification to occur at the blood/material interface. Presented is a summary of our experience (27 studies) with blood pump calcification and a review of the current literature regarding this complication.

An experimental technique for heart-lung transplantation in subprimate models.

The success of heart-lung transplant experiments in subprimate models has been limited because most techniques include total pulmonary denervation, which causes respiratory problems, blood loss, and subsequent death. Using 20 subprimates (12 domestic swine and 8 mongrel dogs), we tested a heterotopic heart-single lung transplant method intended to preserve unilateral pulmonary innervation and to reduce blood loss. After native right pneumonectomy, the donor heart and right lung were transplanted en bloc. Anastomotic sites included the right primary bronchus, the superior vena cava, and the aorta. Selective left bronchial intubation and partial occlusion techniques eliminated the need for cardiopulmonary bypass and mediastinal dissection. All 10 recipient animals survived the operation, and the need for blood transfusions was minimal (1.1 +/- 0.7 [mean +/- SD] units/procedure). Donor and native lung function, assessed by selective left atrial blood gases, were similar: mean PO(2) was 229 +/- 31 mmHg and 180 +/- 25 mmHg, respectively; and mean PCO(2), 36 +/- 13 mmHg and 38+/-2 mmHg, respectively. Nine recipients were weaned from mechanical ventilation with a mean PCO(2) of 38+/-4 mmHg. Preserving unilateral pulmonary innervation allows normal respiration, and minimizing blood loss increases operative survival. Our method of heterotopic heart-single lung transplantation is reliable and could provide a functional heart-lung allograft for conducting future experimental studies of heart-lung transplantation.

Mechanical circulatory assistance: established (IABP) and evolving (LVAD). A narrative summary.

Comparisons of the physiologic bases of intraaortic balloon and extracorporeal or implantable left ventricular assist device or partial artificial heart pumping in experimental and clinical setting are made. The concepts and first principles common and unique to both of these forms of mechanical circulatory support are presented with emphasis on the similarities and important differences. Intraaortic balloon counterpulsation is examined as an intravascular, volume displacement device in series with the systemic circulations. Left ventricular assist devices are analyzed as extravascular in-series or parallel volume-capturing/ejecting devices and as true blood pumps which can be implanted. The interrelated mechanisms of synchronous, diversion/counterpulsation/diastolic augmentation are discussed in relation to quantitative indices of myocardial ischemia, myocardial oxygen supply/demand ratios, the Sarnoff theorem and the Laplace relationship, vis à vis ventricular unloading/impedance reductions. Some of the many clinical settings of IABP are mentioned, along with hydraulic considerations which allow non-invasive determination of stroke volume during clinical IABP mechanical circulatory support. Cardiogenic shock/left ventricular failure/low cardiac output are defined in terms of failure to generate pressure and displace volume and deficits of ejection fraction and stroke volume. Vasodilator therapy (nitroprusside), IABP, and LVAD are then viewed as escalating methods of reversing these deficits. Finally, pressure volume loops of the human left ventricle are compared with those of LVADs, experimentally and clinically, to indicate that LVADs can function and support the circulation during all low output states including ventricular fibrillation and standstill. Representative hemodynamic traces (Fig. 5 and 6) obtained during clinical LVAD trials in man are included to illustrate these theoretical and practical considerations. The use of LVADs in any instance of IABP inadequacy is implicit and inferred.

Comparative in vitro evaluations of vascular graft compliance during dynamic loading.

A prosthetic vascular graft should be nonthrombogenic, compliant with anastomosed vessels and resist excessive dilatation or aneurysm formation. Mechanical performance of a negatively charged, glutaraldehyde-tanned bovine heterograft was evaluated, in vitro, during dynamic loading conditions. The grafts were 16 cm in length with internal diameters of 6 mm (n = 10), 8 mm (n = 12), and 10 mm (n = 8). The prostheses were pneumatically cycled, using intragraft balloons, at a pulse pressure of 120/70 mmHg and a rate of 80 beats/min in 37 degrees C saline for 2.6 million cycles (22.6 days). At selected intervals, the diastolic and pulse volumes of the grafts were measured and compliance calculated. These studies demonstrated that this vascular prosthesis had a high initial compliance, independent of graft diameter. During dynamic loading, diastolic volume increased whereas pulse volume and compliance decreased 12%, 43%, and 49%, respectively (P less than 0.001). Greater than 75% of the changes occurred within 5 days after the onset of testing. Despite these changes, isocompliance was demonstrated for the BioPolyMeric grafts following 22 days of cycling, yielding values similar to those reported for human saphenous vein.

Cardiac transplantation and mechanical circulatory assistance: the Texas Heart Institute experience.

From January 1984 to September 1988, 245 heart transplants were performed at our institution. During this period, 53 staged cardiac transplant procedures were performed using an intraaortic balloon pump (IABP), an extracorporeal centrifugal blood pump (ECBP), an intracorporal left ventricular assist device, and a total artificial heart. Thirty-four (64%) patients underwent subsequent cardiac transplantation and 28 (53%) were discharged. Our data indicate that patients who suffer rapid onset of heart failure and undergo early circulatory support are suitable candidates for successful staged cardiac transplantation. We have also used mechanical support to treat severe heart failure after transplantation, using IABP and ECBP support, as well as an intraarterial axial flow pump. In immunosuppressed patients, infection is the critical issue affecting outcome. There is a need for development of smaller, simpler, less invasive devices with the capacity to provide both systemic and pulmonary circulatory support.

Anatomic considerations for abdominally placed permanent left ventricular assist devices.

To determine anatomic parameters for a permanent, electrically actuated left ventricular assist device (LVAD), the effects of abdominal placement of pneumatic LVADs used as temporary support for patients awaiting heart transplantation was studied. Understanding the anatomic constraints imposed by the abdominal viscera in LVAD placement is crucial, because improper placement can result in compression or obstruction of adjacent structures. Anatomic compatibility was assessed in four men (age 22-48 years) who were supported by the LVAD for over 1 month (range 35-132 days). The pump was intraperitoneally placed in the left upper quadrant. Radiographic techniques were employed, including CT scanning (with patients supine) and contrast imaging (patients in anatomical position), and the pump and conduits appeared to be properly positioned, with minimal compression of the body of the stomach, and no obstruction of adjacent organs. Three patients returned to a solid food diet and exercised daily by stationary cycling and walking. No signs of migration or erosion of the pump were present at the time of LVAD removal and cardiac transplantation. Successful clinical experience with short-term use of the LVAD suggests that the electrically actuated device can be well tolerated in patients requiring permanent left ventricular assistance.

Incidence of perioperative myocardial ischemia detected by different electrocardiographic systems.

To determine the extent to which different electrocardiographic systems account for differences in reported incidence of perioperative myocardial ischemia, the authors simultaneously recorded in 109 patients undergoing coronary artery bypass grafting (CABG) the V5 or modified CM5 lead on five ECG systems by means of a specially constructed common V5 lead. The systems included a Spacelabs Alpha 14 Model Series 3200 ECG Cardule at bandwidths of 0.05-125 Hz and 0.5-30 Hz (a typical operating room monitor), a Marquette Electronics MAC II ECG at 0.05-40 Hz and 0.05-100 Hz (a standard ECG), and a Del Mar Holter recorder at 0.1-100 Hz. Relative ST-segment position and incidence of new ischemia compared to the preoperative ECG were determined in 109 sets of preinduction traces and 877 sets of intraoperative traces. ST-segment position on the three recording systems conforming with the American Heart Association (AHA) low-frequency response recommendations (0.05 Hz) were similar. Compared to the standard ECG, ST-segment position on the Spacelabs at 0.5-30 Hz was consistently more negative. Displacement on the Holter was consistently less negative and less positive. By the 0.1-mV displacement criterion for diagnosis of myocardial ischemia on any one ECG system, 16.5% of patients on arrival and 32.1% of patients intraoperatively suffered new myocardial ischemia. Based on the operating room monitor, arrival and intraoperative ischemia were present in 15.6 and 27.5% of patients, respectively. Ischemia at the same periods was less frequent by the standard ECG system (5.5 and 12.8%, respectively) and least frequent by the Holter recorder (4.6 and 8.3%, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)