Petar Prcevski

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.

Effect of Ibutilide, a New Class III Agent, On Sustained Atrial Fibrillation in a Canine Model of Acute Ischemia and Myocardial Dysfunction Induced By Microembolization

The effect of ibutiJide, a new Class III antiarrhythmic agent, upon acute onset atriai fibriJIation was investigated in a closed‐chest canine model of acute left ventricular fLVj dysfunction. Twenty‐four anesthetized mongrel dogs, mean weight 24.9 ± 4 kg were subjected to coronary artery microsphere emboiization and volume Joading, followed by attempted induction of atrial fihrillation (AF) by rapid atrial pacing. Acute ischemic LV dysfunction was successfully induced by emboiization in aii dogs, and caused significant (P < 0.02) decreases in LV systolic pressure, peak + dp/dt (and − dp/dtj, stroke volume, and RR interval; whereas LV end diastolic pressure and QTc significantiy increased. Sustained AF (≥ 30 min) was successfully induced in 15 of 24 dogs (62%) and unsustained AF (< 30 min) was induced in the remainder (38%). At 30 minutes after induction of sustained AF, 15 dogs were randomized to intravenous ibutiiide (0.15 mg/kg, given as a 0.075 mg/kg bolus, followed by 0.075 mg/kg infusion over 1 hour; n = 7) or placebo (saline; n = 8). There were no statistically significant differences between the ibutilide and the placebo groups with respect to mean LV systolic pressure, LV end diastoJic pressure, LV dp/dt, RR intervaJ, or QTc intervaJ during AF prior to infusion. All seven dogs receiving ibutiJide converted to sinus rhythm after a median of 3 minutes (range 0.5–26 min), whiJe onJy three of eight pJacebo dogs (P < 0.03J converted to sinus rhythm after a median duration of 30 minutes (range 15–60 min) (P < 0.04 for difference in time to conversionj. QTc prolonged by 27 ± 17%, 1 hour after ibutiJide, but was unaJtered after pJacebo (P ≥ 0.02). There were no significant hemodynamic changes after either ibutiJide or pJacebo. We concJude that: (1) sustained AF (> 30 min) can be readily induced in this closed‐chest animal model and used t o test antiarrhythmic agents acutely; and (2) intravenous ibutiJide is effective in rapidJy terminating acute onset AF; the drug prolongs the QTc intervaJ but does not exacerbate preexisting hemodynamic compromise in the acutely ischemic LV.

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.

Aqueous oxygen near the homogeneous nucleation limit of water: stabilization with submicron capillaries.

Previous studies have demonstrated that the metastability threshold of aqueous oxygen (AO) is inversely dependent on the internal diameter of capillary tubes used to deliver it into blood. The hypothesis was tested herein that significantly higher thresholds are attainable with capillaries having markedly smaller dimensions (submicron) than those previously studied. Water was equilibrated with oxygen over a 0.3- to 0.7-kbar range. Inert gases (argon, helium) facilitated studies at pressures to 2.5 kbar. An argon-ion laser was used to visualize fluorescein in the liquid effluent from silica capillaries that were tapered at the distal end to a submicron internal diameter (0.5 ± 0.3 microns). During infusion of the fluorescent effluent into host water at 21° C and atmospheric pressure, integrity of the effluent and lack of microbubbles were monitored by videomicroscopy. No microbubbles were noted at AO concentrations ranging from 7.5 to 12.8 ml O2/g (0.34 to 0.68 kbar, respectively) or in the aqueous argon effluent at concentrations to 14 ml Ar/g (0.75 kbar). For aqueous helium, effluent nucleation was not observed at a mean concentration of 13 ± 3 ml He/g (2.0 ± 0.5 kbar), with an upper value of 15.2 ml He/g (2.4 kbar). The data represent the highest values of the tensile strength of water ever observed and approximate its theoretical homogeneous nucleation limit. Thus, remarkably high metastable concentrations of AO and other gases are attainable with the use of submicron capillaries.