Ali D. Spanta

Aqueous Oxygen A Highly O2-Supersaturated Infusate for Regional Correction of Hypoxemia and Production of Hyperoxemia

BACKGROUND High levels of hyperoxemia may have utility in the treatment of regional tissue ischemia, but current methods for its implementation are impractical. A catheter-based method for infusion of O2, dissolved in a crystalloid solution at extremely high concentrations, ie, 1 to 3 mL O2/g (aqueous oxygen [AO]), into blood without bubble nucleation was recently developed for the potential hyperoxemic treatment of regional tissue ischemia. METHODS AND RESULTS To test the hypotheses that hypoxemia is correctable and that hyperoxemia can be produced locally by AO infusion, normal saline equilibrated with O2 at 3 MPa (30 bar; 1 mL O2/g) was delivered into arterial blood in two different animal models. In 15 New Zealand White rabbits with systemic hypoxemia, AO was infused into the midabdominal aorta at 1 g/min. Mean distal arterial PO2 increased to 236+/-113 and 593+/-114 mm Hg on 1-hour periods of air and O2 breathing, respectively, from a baseline of 70+/-10 mm Hg (P<.01). In contrast, infusion of ordinary normal saline in a control group (n=7) had no effect on arterial PO2. No differences between groups (P>.05) in temporal changes in blood counts and chemistries were identified. In 10 dogs, low coronary blood flow in the circumflex artery was delivered with a roller pump through the central channel of an occluding balloon catheter. Hypoxemic, normoxemic, and AO-induced hyperoxemic blood perfusates (mean PO2, 52+/-4, 111+/-22, and 504+/-72 mm Hg, respectively) were infused for 3-minute periods in a randomized sequence. Short-axis two-dimensional echocardiography demonstrated a significant decrease (P<.05) in left ventricular ejection fraction compared with baseline physiological values with low-flow hypoxemic and normoxemic perfusion but not with low-flow hyperoxemic perfusion. CONCLUSIONS Intra-arterial AO infusion was effective in these models for regional correction of hypoxemia and production of hyperoxemia.

Aqueous Oxygen Attenuation of Reperfusion Microvascular Ischemia in a Canine Model of Myocardial Infarction

Uncorrected microvascular ischemia may contribute to left ventricular impairment during reperfusion after prolonged coronary artery occlusion. Attenuation of such ischemia in microvessels with impaired erythrocyte flow may require delivery of oxygen at high levels in plasma. Intraarterial infusion of aqueous oxygen (AO) can be used in a site specific manner to achieve hyperoxemic levels of oxygenation in the perfusate. With this new approach, the hypothesis was tested that reperfusion microvascular ischemia can be attenuated.After a 90 min coronary balloon occlusion in a canine model, AO hyperoxemic intracoronary perfusion was performed for 90 min after a 30 min period of autoreperfusion. Control groups consisted of normoxemic reperfusion, both passive (autoreperfusion) and active (roller pump). A significant improvement in left ventricular ejection fraction (p < 0.05) at 2 hr of reperfusion was noted only in the AO hyperoxemia group (17 ± 6% by two dimensional echo), without a significant reduction in the improvement 1 hr after termination of treatment. During AO hyperoxemic perfusion, ECG ST segment isoelectric deviation normalized, and frequency of ventricular premature contractions was significantly reduced, in contrast to the autoreperfusion control group (p < 0.05). Microvascular blood flow, measured as the ischemic/normal left ventricular segment ratio by radiolabeled microspheres immediately after AO hyperoxemic perfusion, was double the value of the autoreperfusion control group at 2 hr of reperfusion (p < 0.05).We conclude that reperfusion microvascular ischemia is attenuated by intracoronary AO hyperoxemic perfusion and acutely improves left ventricular function in this model.

Chronic morphologic changes of skeletal muscle ventricles in circulation

Skeletal muscle ventricles (SMVs) were constructed either extrathoracically or intrathoracically in 44 dogs using the left latissimus dorsi muscle. These SMVs functioned as aortic counterpulsators for from several hours to 216 days. In this study, the relationship between the morphologic changes in the SMVs and their time course in the circulation was evaluated retrospectively. The average volume of the SMV chamber after it had been excised and fixed in formalin was 21.3 +/- 11.0 mL (mean +/- the standard deviation) for extrathoracic SMVs and 20.0 +/- 7.5 mL for intrathoracic SMVs. The volume of the SMV chamber did not correlate with the time course in the circulation. The SMV wall was mainly composed of three components: muscular, fibrous, and fatty aspects. The overall thickness of the wall appeared to be preserved over time in the circulation. However, the thickness of the muscular component tended to decrease over time. SMV rupture occurred in 15 dogs between postoperative days 4 and 39. All ruptures occurred at the suture line between the SMV and the vascular conduits. There was some degree of thrombus in 24 SMVs. Before SMVs can be applied clinically for the purpose of cardiac assist, problems with rupture and thrombus formation must be solved. A better understanding of the morphologic changes that take place in the SMV over time also is needed.

Skeletal muscle ventricles with improved thromboresistance : 28 weeks in circulation

Skeletal muscle ventricles (SMVs) were constructed from the left latissimus dorsi in 22 mongrel dogs. The configuration of these SMVs was different from those previously reported. The animals were divided into two groups: group A (n = 11) SMVs rested for 10 weeks after construction; group B (n = 11) SMVs rested for 18 weeks. At the end of the delay period, SMVs were tested in vivo with a mock circulation device. The SMVs in group B developed stroke work greater than those in group A. After acute testing, SMVs (n = 12) were connected to the descending thoracic aorta and stimulated to contract during diastole. Aortic diastolic counterpulsation was achieved in all dogs, with 9 animals surviving from 1 to beyond 28 weeks. In all of the dogs surviving 1 week or more, the SMVs remained free of thrombus. Aspirin was used as the only antithrombotic agent. Skeletal muscle ventricles in this study were able to develop stroke work similar to that previously reported, intermediate between that of the right and left ventricular stroke work, with a significantly decreased incidence of thromboembolism.

Skeletal Muscle Ventricles, Left Ventricular Apex-to-Aorta Configuration 1 to 11 Weeks in Circulation

BACKGROUND Skeletal muscle ventricles (SMVs) have been used in animals in a variety of configurations to provide circulatory assistance. Long-term survival and function have been demonstrated. Our laboratory recently obtained promising short-term hemodynamic data in a left ventricular apex-to-aorta model. METHODS AND RESULTS SMVs were constructed from the left latissimus dorsi muscle in five adult mongrel dogs. After a 3-week period of vascular delay and 5 to 7 weeks of electrical conditioning, valved conduits were used to connect the left ventricular apex to the SMV and the SMV to the descending aorta. The SMV was then stimulated to contract during cardiac diastole. Initial measurements showed a significant increase in the mean femoral diastolic pressure (62 +/- 6 versus 51 +/- 5 mm Hg, P < .05). There was also a decrease in the left ventricular tension-time index (11.5 +/- 2.5 versus 14.6 +/- 2.1 mm Hg.s, P < .05), indicating a decrease in the work requirement of the left ventricle. During SMV stimulation, the majority of flow (65%) was through the SMV circuit and was associated with reversal of flow in the proximal descending thoracic aorta. The longest-surviving animal survived 76 days, at which time pressure augmentation was still seen (mean femoral diastolic pressure, 63 +/- 0.9 versus 50 +/- 1.2 mm Hg, P < .05). CONCLUSIONS Survival beyond the acute setting is possible with this model. Diastolic pressure augmentation can be effectively maintained over time.

Autologous Skeletal Muscle, an Alternative for Cardiac Assistance

Original attempts to use skeletal muscle for cardiac assistance were soon abandoned when the problem of muscle fatigue could not be solved. In the last 2 decades, better understanding of muscle physiology and the development of successful protocols of electrical muscle conditioning have given new impetus to researchers around the world to proceed in the effort to identify useful applications of skeletal muscle to support the heart. More than 100 patients around the world have undergone cardiomyoplasty, mostly for cardiac failure. While subjective improvement in symptoms was noticed in the majority of the patients, only recently favorable hemodynamic changes have been documented. The other alternative that has been pursued in the laboratory is the construction of skeletal muscle ventricles that, after conditioning and vascular delay, have been shown to provide significant cardiac support when used for diastolic counterpulsation or for right heart bypass in animal models.