Hemodynamic response to in situ latissimus dorsi muscle stimulation: implications in dynamic cardiomyoplasty.

Dynamic cardiomyoplasty (DCM) involves the electrical stimulation of a pedicled latissimus dorsi muscle flap wrapped around the falling ventricle as a means of cardiac assist. To further elucidate a potential neurohumoral mechanism for improvement of cardiac output after myoplasty, we evaluated the hemodynamic effects of in situ stimulation of the latissimus dorsi muscle (in the absence of cardiomyoplasty). In seven mongrel dogs, a nerve cuff electrode (Medtronic 6901) was placed around the left thoracodorsal nerve (TDN). This was attached to a pulse generator (Medtronic, Itrel 7420), delivering a 4.0 volt, 0.19 second on, 0.81 second off, 33 Hz, 210 microsecond pulse width, cyclic bursts similar to that used in DCM. Stroke volume index (SVI) and other hemodynamic parameters as well as plasma norepinephrine (NE) levels were measured at five stages: baseline, stimulator on at 0, 2, and 5 minutes, and stimulator off at 30 minutes after. The animals were then subjected to 4 weeks of rapid pacing at 240 beats/min (Medtronic 8329) to induce heart failure, and as the rapid pacing was discontinued, measurements were repeated as above. After rapid pacing, cardiac function was significantly depressed, and NE was elevated (133 +/- 69 versus 500 +/- 353 pg/mL, p < 0.05). In the normal hearts, TDN stimulation increased SVI, heart rate, systemic pressure, and NE levels. In heart failure, however, no significant changes in cardiac function and NE levels were noted. In conclusion, our data indicate that in the normal hearts, afferent impulses from TDN stimulation alone may augment cardiac function by means of a neurohumoral effect that is not seen in severe heart failure. The implications of these findings in DCM are discussed.

Character of shed blood in cardiac and thoracic surgery patients: implications for reinfusion.

OBJECTIVE: To determine whether the independently observed increase in the levels of cardiac enzymes in peripheral blood can be accounted for by elevations from postoperative shed-blood reinfusion in patients who have undergone cardiac or thoracic operations. DESIGN: Prospective, case-controlled study. SETTING: A cardiothoracic surgery unit at a university referral centre. PATIENTS: Thirty-four consecutive patients who underwent cardiac or thoracic surgery within a 3-week period. INTERVENTIONS: Coronary artery revascularization (23 patients), cardiac valve replacement or repair (4) and lung resection (7). MAIN OUTCOME MEASURES: Determination of levels of cardiac enzymes and isoenzymes in samples of peripheral and shed blood. Statistical comparison was by paired t-tests within groups and by unpaired t-tests between groups. RESULTS: Serum levels of creatine kinase, lactic dehydrogenase and aspartate aminotransferase were significantly (p < 0.001) elevated in samples of shed blood compared with peripheral blood in all groups. The elevations were found to be related to skeletal muscle injury and were not of cardiac origin. In the absence of myocardial infarction, cardiac isoenzyme levels were significantly (p < 0.001) elevated in the peripheral blood of cardiac surgery patients compared with that of thoracic surgery patients. CONCLUSION: Reinfusion of shed blood will result in elevated levels of cardiac enzymes in peripheral blood but will not increase the percentage of isoenzymes.

Conformational adaptation of muscle: implications in cardiomyoplasty and skeletal muscle ventricles.

In dynamic cardiomyoplasty and other forms of muscle-powered cardiac assist, the stretch that should be applied to the skeletal muscle to obtain optimal resting tension remains unclear. To test the hypothesis that skeletal muscle is capable of conformational adaptation over time, the effect of altered resting tension on the chronic performance of a skeletal muscle ventricle was studied. In 7 mongrel dogs, skeletal muscle ventricles constructed from the lastissimus dorsi muscle were stimulated to contract for 12 weeks against an implantable mock circulation. The preload pressure was altered, thereby varying the resting tension of the latissimus dorsi. One group (group I; n = 5) was maintained at a preload of 80 mm Hg, whereas a second group (group II; n = 2) was maintained at 20 mm Hg. Adaptation to preload was observed. After 12 weeks, the pressure increase generated by the skeletal muscle ventricle at a preload of 20 mm Hg was only 35 +/- 2 mm Hg for group I compared with 44 +/- 5 mm Hg for group II. At a preload of 80 mm Hg, the pressure increase was 61 +/- 4 mm Hg for group I and only 34 +/- 6 mm Hg for group II. Adaptation of the latissimus dorsi to a new resting tension has important implications in the use of skeletal muscle for cardiac assist. Stretching the latissimus dorsi to its in situ length during cardiomyoplasty is not required for future muscle performance to be optimal.

Effects of hypothermia on hemodynamic responses to dopamine and dobutamine.

Hemodynamic characteristics, arrhythmogenicity, and dose-related hemodynamic responses to intravenous dopamine (group I) and dobutamine (group II) were examined in 16 swine at three different core body temperatures (38.5 degrees C, 35 degrees C, and 30 degrees C). The animals were anesthetized with isoflurane and mechanically ventilated. Cooling and re-warming were accomplished by a femoral-jugular A-V shunt. The animals were cooled down to 30 degrees C and stabilized for 1 hour before intravenous infusion of dopamine (group I, n = 8) or dobutamine (group II, n = 8) was started at 2, 5, 10, 15, 20, and 30 micrograms/kg/min. Hemodynamic responses to the two inotropes were continuously monitored with a bedside monitor equipped with a PC mode for customized data collection and analysis. Computerized arrhythmia detection was performed. Our findings were: (1) profound hypothermia (30 degrees C) causes significant depression of hemodynamic functions; (2) IV infusion of dopamine and dobutamine can be used safely and effectively for inotropic support during profound hypothermia, and the optimal dosage for improving cardiac output is 10-20 micrograms/kg/min; (3) no risk of inducing arrhythmia was noted with IV infusion of both inotropes up to a maximum dosage of 30 micrograms/kg/min, even though significant sinus tachycardia was consistently seen at 30 micrograms/kg/min.

Biochemical and functional correlates of myocardium-like transformed skeletal muscle as a power source for cardiac assist devices.

Skeletal muscles, such as the latissimus dorsi muscle, can be transformed to gain considerable fatigue resistance to be suitable either for cardiomyoplasty, or to power a cardiac assist device. Such transformation of the skeletal muscle can be achieved by low frequency electrical stimulation for several weeks. In this article, we reviewed the stimulation protocol, and subsequent histochemical, biochemical, and functional changes in the skeletal muscle, and compared them to those of the cardiac muscle. The parameters that should be useful for stimulating such a muscle to assist the heart are defined. The issues currently under study, including the optimal transformation parameters, the feasibility of working transformation, and the importance of device design to minimize vascular compromise of the muscle, are also discussed. It is concluded that there is a great potential to use the plasticity of skeletal muscle for clinical purposes, specifically by transforming the skeletal muscle to resemble the myocardium in order to use it either to replace or repair the myocardium, or as the endogenous power source for a cardiac assist device.

The effects of electrical stimulation on denervated muscle using implantable electrodes.

This experimental study investigated the effects of continuous electrical stimulation on denervated muscle. The canine peroneal nerve was severed and repaired microsurgically, and the denervated extensor muscle group of the leg was stimulated continuously with an implantable electrode and pulse generator. EMG study, muscle force measurement, muscle weight measurement, histology, and histochemistry were performed to study the effect at eight weeks after the operation. Continuous electrical stimulation (pulse frequency 130 pps, burst rate approximately 1 train/min) was effective in decreasing muscle atrophy and in improving muscle force. These findings may have broader clinical applications.

The muscle-powered dual-chamber counterpulsator: rheologically superior implantable cardiac assist device.

To enable long-term studies of a totally implantable cardiac assist device powered by transformed fatigue-resistant skeletal muscle, we developed a dual-chamber extraaortic counterpulsator implanted, 2 of which fluid for power transfer. Six dogs had our dual-chamber extraaortic counterpulsator implanted, 2 of which had undergone prior transformation of their latissimus dorsi muscle. The blood pump, with a Dacron graft at each end, was anastomosed end-to-side and parallel to the thoracic aorta, allowing continuous blood flow to minimize thrombus formation caused by stasis and turbulence. The blood pump was powered by a hydraulic bulb placed beneath the latissimus dorsi muscle. The latissimus dorsi muscle was stimulated to contract during diastole using a synchronized burst electrical stimulator. The ratio of diastolic pressure time product over systolic time tension index, which reflects the myocardial oxygen supply and demand ratio, was calculated from ascending aortic pressure tracings. A consistent increase in this ratio of 44% in 4 dogs with nontransformed latissimus dorsi muscle and of 70% in 2 dogs with transformed latissimus dorsi muscle was obtained when the device was activated. Preliminary chronic implantation studies using a Medtronic cardiomyostimulator (Model SP1005) as the burst stimulator for our dual-chamber extraaortic counterpulsator produced an average augmentation in aortic diastolic pressure of 34 mm Hg for up to six days. Our results indicate that, with further refinement of this device, a long-term totally implantable cardiac assist device powered by endogenous skeletal muscle will be feasible.

Myocardial protection: heparin-induced free fatty acid elevation during cardiopulmonary bypass and its prevention.

Elevated serum free fatty acids (FFA) adversely affect the hypoxic or ischemic myocardium by impairing cardiac function, decreasing contractility, and increasing arrhythmogenicity . Heparin, an anticoagulant used routinely in cardiac surgery, elevates circulating FFA. The purpose of this study was to determine the magnitude of FFA elevation in cardiac surgery patients and to establish, in dogs, a dose-response of FFA to heparin and to test whether glucose-insulin-potassium (GIK) solution could prevent heparin-induced rise in FFA. In 52 patients undergoing cardiopulmonary bypass (CPB), serial blood samples were obtained for FFA determination before and after heparin (300 IU/kg) administration. Then in seven normal dogs, heparin at a dose of 80 or 300 IU/kg was given. In another group of five dogs either GIK solution or NaCl were infused, while intravenous heparin (300 IU/Kg) injection was given. Each dog acted as its own control. It was found that there was a twofold increase in circulating serum FFA after heparin administration during cardiac surgery in patients, reaching the toxicity level of greater than 0.80 meq/liter. One-third of these patients had elevations of FFA level above the arrhythmogenic threshold of greater than 1.20 meq/liter. In the canine experiments low-dose heparin (80 IU/Kg) resulted in milder elevations of FFA for a shorter duration. Dogs given saline and high-dose heparin (300 IU/Kg) had responses similar to those seen in human patients undergoing cardiac surgery, while GIK abolished the elevation of serum FFA in response to high-dose heparin, eventually reducing FFA to below preheparin levels.

The pulmonary effects of opiate blockade in septic shock.

Sepsis remains the most common associated factor in acute respiratory failure (ARF). Endogenous opiates are known to have both respiratory and cardiovascular depressant effects. Because there is a high level of circulating endogenous opiates in sepsis, the possible role of opioids in the ARF syndrome seen in sepsis was studied. Sixteen piglets were infused with an LD100 dose (7.5 X 10(10) organisms/kg) of live Escherichia coli (Type 09-41). The pigs were hemodynamically monitored. Serial blood samples were taken for arterial blood gases and lactate. Serial lung biopsies were taken for determining wet/dry lung weight ratios and for histology. Group I (n = 8): septic shock controls without naloxone; group II (n = 8): naloxone treated, given as 2 mg/kg/hr intravenous boluses, starting within 1 min of E. coli infusion. All animals died of septic shock. Survivors at 150 min in group II had a higher blood pressure than group I (67.7 +/- 5.33 SEM vs 39.0 +/- 9.39) and cardiac output was also greater (1.07 +/- 0.23 vs 0.25 +/- 0.25). By 210 min, group I had no survivors (0/8) while 3/8 in group II survived. Pulmonary vascular resistance in group II at 90 and 120 min (870.8 +/- 274.1 and 942.5 +/- 12.9, respectively) was lower than in group I (2868.3 +/- 843.6 and 4156 +/- 1067). The PO2 was markedly better in group II and at 90 min; controls had a PO2 70.7 +/- 13.0, while group II had a PO2 111.4 +/- 8.4 (P less than 0.05). PCO2 levels showed a progressive rise in group I from 39.25 +/- 1.4 to 49.4 +/- 8.57.(ABSTRACT TRUNCATED AT 250 WORDS)