Biomedical subjects

J Luis Guerrero

Publications and source records attributed to J Luis Guerrero.

16 recordsLinked to original sources

PubMed2006

Chordal cutting does not adversely affect left ventricle contractile function.

BACKGROUND: Severing a limited number of second-order chordae to the anterior leaflet can improve ischemic mitral regurgitation (MR). Some concerns have been raised regarding possible influence on regional and global left ventricle (LV) function. We evaluated changes in cardiac function in 5 normal sheep with cutting of pre-instrumented chords in the beating heart to maintain constant load. METHODS AND RESULTS: Under cardiopulmonary bypass, wires were placed around the 2 central basal chordae and brought outside the heart, which was restarted. Hemodynamic and imaging data were collected before and after chordal cutting by radiofrequency ablation using those wires. Segmental contractility was assessed invasively using sonomicrometers and noninvasively using Doppler tissue velocity and strain rate (with strain rate viewed as less load-dependent than ejection fraction) at 6 sites: base, mid-ventricle, and apex along the anteroseptal and posterolateral walls. We found no changes from before to after chordal cutting in LV end-diastolic volume (47.2+/-3.3 after cutting versus 48.4+/-4.6 mL before cutting, P=0.66), end-systolic volume (21.5+/-1.2 versus 22.3+/-2.8 mL, P=0.68), ejection fraction (54.2+/-1.8 versus 54.2+/-2.7%, P=0.96), systolic ventricular elastance (7.28+/-1.68 versus 7.66+/-2.11 mm Hg/mL, P=0.64), preload-recruitable stroke work (46.6+/-7.7 versus 50.2+/-10.7 mm Hg, P=0.76), and LVdP/dt (1480+/-238 versus 1392+/-250 mm Hg/s, P=0.45). Doppler tissue velocities and longitudinal strain rates surrounding the papillary muscles were unchanged, as were sonomicrometer longitudinal and mediolateral absolute strains. No wall motion abnormalities were visible around the papillary muscles, and no MR developed. CONCLUSIONS: We find no evidence for acutely decreased global or segmental LV contractility with chordal cutting. This absence of adverse effects is consistent with long-term clinical experience with cutting these chords in valve repair.

Animals↗

PubMed2006

Sildenafil improves coronary artery patency in a canine model of platelet-mediated cyclic coronary occlusion after thrombolysis.

OBJECTIVES: We sought to assess the effect of sildenafil, a highly-specific type 5 phosphodiesterase (PDE5) inhibitor, on platelet-mediated cyclic coronary flow reductions occurring in a canine model of coronary thrombosis despite aspirin therapy. BACKGROUND: The PDE5 inhibitors augment the antithrombotic effects of nitric oxide in vitro and in vivo, but it has been proposed that the PDE5 inhibitor sildenafil is prothrombotic. METHODS: Cyclic coronary flow reductions were induced in the left anterior descending coronary artery by creation of a stenosis, endothelial injury, and thrombus formation followed by treatment with aspirin, heparin, and tissue plasminogen activator. After an initial observation period, dogs were treated with or without sildenafil (100 microg/kg bolus followed by 4 microg/kg/min infusion). RESULTS: Cyclic coronary flow reductions ceased in five of six animals 18 +/- 5 min after initiation of sildenafil but continued in all six control animals. The portion of the observation period during which the coronary artery was patent increased from 52 +/- 9% to 83 +/- 5% after sildenafil administration (p = 0.008) but did not differ between the first and second observation periods in untreated dogs (49 +/- 11% vs. 44 +/- 11%, respectively). Among animals with plasma free sildenafil levels > or =20 nmol/l, cyclic coronary flow reductions were 73 +/- 12% less frequent and the time to cessation of cycling 72 +/- 14% shorter than in animals with levels <20 nmol/l (p < 0.05 for both). Sildenafil transiently decreased blood pressure 7 +/- 1% but did not change heart rate. Sildenafil treatment reduced ex vivo thrombin-induced platelet aggregation by 39 +/- 3% (p < 0.005). CONCLUSIONS: Sildenafil improves coronary patency in a canine model of platelet-mediated coronary artery thrombosis, likely via inhibition of platelet aggregation.

Animals↗

PubMed2005

Quantitative assessment of regional myocardial function in mice by tissue Doppler imaging: comparison with hemodynamics and sonomicrometry.

BACKGROUND: Tissue Doppler imaging (TDI) is a novel echocardiographic method to quantify regional myocardial function. The objective of this study was to assess whether myocardial velocities and strain rate (SR) could be obtained by TDI in mice and whether these indices accurately quantified alterations in left ventricular (LV) systolic function. METHODS AND RESULTS: TDI was performed in 10 healthy mice to measure endocardial (v(endo)) and epicardial systolic velocities and SR. In further experiments, TDI indices were compared with dP/dt(max) and with sonomicrometer-derived regional velocities, at rest and after administration of dobutamine or esmolol. TDI indices were also studied serially in 8 mice before and 4 and 7 hours after endotoxin challenge. Myocardial velocities and SR were obtained in all mice with low measurement variability. TDI indices increased with administration of dobutamine (v(endo) from 2.2+/-0.3 to 3.8+/-0.2 cm/s [P<0.01]; SR from 12+/-2 to 20+/-2 s(-1) [P<0.05]) and decreased with administration of esmolol (v(endo) 1.4+/-0.2 cm/s [P<0.05]; SR 6+/-1 s(-1) [P<0.01]). Both indices correlated strongly with dP/dt(max) (r2=0.79 for SR and r2= 0.69 for v(endo); both P<0.0001). SR and shortening fraction were predictors of dP/dt(max) even after adjustment for the confounding effect of the other variables. V(endo) correlated closely with sonomicrometer-measured velocity (r2=0.71, P<0.0005). After endotoxin challenge, decreases in both v(endo) and SR were detected before decreases in shortening fraction became manifest. CONCLUSIONS: Myocardial velocities and SR can be measured noninvasively in mice with the use of TDI. Both indices are sensitive markers for quantifying LV global and regional function in mice.

Animals↗

PubMed2005

In vivo gene transfer of parvalbumin improves diastolic function in aged rat hearts.

OBJECTIVE: Diastolic dysfunction is a characteristic finding of the aged mammalian heart. Parvalbumin acts as a Ca2+ sink and enhances relaxation in skeletal muscle, and overexpression of parvalbumin in myocardium increased cardiac relaxation in vitro as well as in vivo. Therefore, the objective of this study is to test the hypothesis that in vivo gene transfer of parvalbumin will improve diastolic dysfunction in aged rat heart. METHODS: We used adenovirus to transfer parvalbumin into two different rat models of aging: the Fischer 344 (F344) and the Fischer 344 x Brown Norway F1 hybrid (F344 x BN). Cardiac function was measured and compared after gene transfer. RESULTS: In vivo overexpression of parvalbumin in both rat aging models had no effect on systolic parameters but reduced left ventricular diastolic pressure and the time course of pressure decline. Overexpression of parvalbumin also improved the force frequency relationship in senescent rats. CONCLUSION: In vivo overexpression of parvalbumin improves diastolic dysfunction in two rat models of senescence, and this effect is independent of the rat strain investigated. The results show promise that gene therapy of parvalbumin may address the impaired Ca2+ homeostasis and diastolic dysfunction without an increase in energy expenditure.

Adenoviridae↗

PubMed2005

Enhancement of cardiac function and suppression of heart failure progression by inhibition of protein phosphatase 1.

Abnormal calcium cycling, characteristic of experimental and human heart failure, is associated with impaired sarcoplasmic reticulum calcium uptake activity. This reflects decreases in the cAMP-pathway signaling and increases in type 1 phosphatase activity. The increased protein phosphatase 1 activity is partially due to dephosphorylation and inactivation of its inhibitor-1, promoting dephosphorylation of phospholamban and inhibition of the sarcoplasmic reticulum calcium-pump. Indeed, cardiac-specific expression of a constitutively active inhibitor-1 results in selective enhancement of phospholamban phosphorylation and augmented cardiac contractility at the cellular and intact animal levels. Furthermore, the beta-adrenergic response is enhanced in the transgenic hearts compared with wild types. On aortic constriction, the hypercontractile cardiac function is maintained, hypertrophy is attenuated and there is no decompensation in the transgenics compared with wild-type controls. Notably, acute adenoviral gene delivery of the active inhibitor-1, completely restores function and partially reverses remodeling, including normalization of the hyperactivated p38, in the setting of pre-existing heart failure. Thus, the inhibitor 1 of the type 1 phosphatase may represent an attractive new therapeutic target.

Animals↗

PubMed2004

Abrogation of ventricular arrhythmias in a model of ischemia and reperfusion by targeting myocardial calcium cycling.

Abnormal intracellular Ca(2+) cycling plays an important role in cardiac dysfunction and ventricular arrhythmias in the setting of heart failure and transient cardiac ischemia followed by reperfusion (I/R). We hypothesized that overexpression of the sarcoplasmic reticulum Ca(2+) ATPase pump (SERCA2a) may improve both contractile dysfunction and ventricular arrhythmias. Continuous ECG recordings were obtained in 46 conscious rats after adenoviral gene transfer of either SERCA2a or the reporter gene beta-galactosidase (beta gal) or parvalbumin (PV), as early as 48 h before and 48 h after 30 min ligation of the left anterior descending artery by using an implantable telemetry system. Sham-operated animals were used for comparison for hemodynamic measurements, whereas within-animal baseline was used for electrocardiographic and echocardiographic parameters. All episodes of nonsustained ventricular tachycardia (VT) and ventricular fibrillation (VF) were counted, and their durations were summed by telemetry. I/R decreased regional cardiac wall thickening as well as the maximal rate of left ventricular pressure rise (+dP/dt) and ventricular pressure fall (-dP/dt). SERCA2a restored regional wall thickening and +dP/dt and -dP/dt to levels seen preoperatively. Regional-wall motion and anterior-wall thickening were improved in the SERCA2a animals, as assessed by echocardiography and piezoelectric crystals. To assess whether these effects are SERCA2a specific, we overexpressed a skeletal-muscle protein, PV, to examine whether Ca(2+) buffering alone can mitigate ventricular arrhythmias. During the first hour after I/R, the rate of nonsustained VT plus VF was 16 +/- 5 episodes per h (n = 6) in the Ad.beta gal group, 22 +/- 6 in the Ad.PV group, and 4 +/- 2(n = 6, P < 0.01) in the Ad.SERCA2a group. The decrease in VT plus VF in the Ad.SERCA2a group was consistent throughout the 48 h of monitoring. These results show that improving intracellular Ca(2+) handling by overexpression of SERCA2a restores contractile function and reduces ventricular arrhythmias during I/R.

Animals↗

PubMed2004

Clot lysis in a primate model of peripheral arterial occlusive disease with use of systemic or intraarterial reteplase: addition of abciximab results in improved vessel reperfusion.

PURPOSE: This study was designed to compare the ability of reteplase (a fibrinolytic agent) alone or in combination with abciximab (a monoclonal antibody antagonist of platelet glycoprotein IIb/IIIa) to achieve and sustain vessel patency in an acute model of peripheral arterial occlusive disease in cynomolgus monkeys. MATERIALS AND METHODS: Total arterial occlusion was induced in the femoral arteries of 32 cynomolgus monkeys (eight groups of four) by endothelial injury and injection of thrombin-treated autologous blood. Reteplase was administered by intravenous bolus dose or by intraarterial infusion at the site of the clot. Abciximab was administered as a single weight-adjusted intravenous bolus dose. Platelet activity was measured by ex vivo platelet aggregation before and after abciximab treatment. Different groups of animals received sequential partial doses of reteplase with or without increasing doses of abciximab until either the weight-adjusted human dose equivalent of reteplase was reached or vessel recanalization was achieved. RESULTS: Animals receiving reteplase-only regimens demonstrated variability in the times required for reperfusion and the permanence of the effect. The coadministration of abciximab at doses of the antibody that achieved near or full inhibition of platelet function generally decreased the time to reperfusion and resulted in more consistent and sustained vessel patency. In the case of systemic intravenous reteplase, the coadministration of abciximab resulted in effective reperfusion of thrombosed vessels at decreased doses of the lytic agent. CONCLUSIONS: Reteplase administered systemically or at the site of thrombotic occlusion restored blood flow for periods of varying duration in monkeys with acute femoral artery thrombosis. The coadministration of systemic intravenous abciximab to intravenous or intraarterial reteplase allowed the use of lower doses of fibrinolytic agent with more accelerated and sustained reperfusion.

Abciximab↗

PubMed2003

Efficacy of chordal cutting to relieve chronic persistent ischemic mitral regurgitation.

BACKGROUND: Mitral regurgitation (MR) conveys adverse prognosis in ischemic heart disease. Leaflet closure is restricted by tethering to displaced papillary muscles, and is, therefore, incompletely treated by annular reduction. In an acute ischemic model, we reduced such MR by cutting a limited number of critically positioned chordae to the leaflet base that most restrict closure but are not required to prevent prolapse. Whether this is effective without prolapse, recurrent MR, or left ventricular (LV) failure in chronic persistent ischemic MR, despite greater LV remodeling, remains to be established. Therefore, we studied 7 sheep with chronic inferobasal infarcts known to produce progressive MR over 2 months. In all of those sheep, after a mean of 4.1 months, the 2 central basal (intermediate) chordae were cut at the chronic ischemic MR stage. 3-Dimensional echo quantified MR, LV function, and valve geometry. Five other sheep were followed for a mean of 7.8+/-1.2 months after inferobasal infarction with chordal cutting. RESULTS: All 7 of the sheep with chronic ischemic MR (increased from 1.4+/-0.4 to 11.1+/-0.5 mL/beat, regurgitant fraction=39.0+/-4.2%, P<0.0001) showed anterior leaflet angulation at the basal chord insertion. Although end-systolic volume had doubled, cutting the 2 central basal chordae significantly decreased the MR to baseline (P<0.0001) without prolapse or decline in EF (41.1+/-1.5% to 42.6+/-1.6%, P=not significant [NS]). The five sheep with long-term follow-up showed no prolapse or MR, and no significant post-infarct decrease in LV ejection fraction (EF; 38.9+/-2.4% to 41.4+/-1.2%, P=NS). CONCLUSIONS: Cutting a minimum number of basal (intermediate) chordae can improve coaptation and reduce chronic persistent ischemic MR without impairing LVEF. No adverse effects were noted long-term after chordal cutting at the time of infarction.

Animals↗

PubMed2003

Deletion of cytosolic phospholipase A2 promotes striated muscle growth.

Generation of arachidonic acid by the ubiquitously expressed cytosolic phospholipase A2 (PLA2) has a fundamental role in the regulation of cellular homeostasis, inflammation and tumorigenesis. Here we report that cytosolic PLA2 is a negative regulator of growth, specifically of striated muscle. We find that normal growth of skeletal muscle, as well as normal and pathologic stress-induced hypertrophic growth of the heart, are exaggerated in Pla2g4a-/- mice, which lack the gene encoding cytosolic PLA2. The mechanism underlying this phenotype is that cytosolic PLA2 negatively regulates insulin-like growth factor (IGF)-1 signaling. Absence of cytosolic PLA2 leads to sustained activation of the IGF-1 pathway, which results from the failure of 3-phosphoinositide-dependent protein kinase (PDK)-1 to recruit and phosphorylate protein kinase C (PKC)-zeta, a negative regulator of IGF-1 signaling. Arachidonic acid restores activation of PKC-zeta, correcting the exaggerated IGF-1 signaling. These results indicate that cytosolic PLA2 and arachidonic acid regulate striated muscle growth by modulating multiple growth-regulatory pathways.

3-Phosphoinositide-Dependent Protein Kinases↗

PubMed2002

Reverse ventricular remodeling reduces ischemic mitral regurgitation: echo-guided device application in the beating heart.

BACKGROUND: In ischemic mitral regurgitation (MR), mitral leaflet closure is restricted by ventricular remodeling with displacement of the papillary muscles (PMs). Therapy is uncertain because ring annuloplasty does not alleviate PM displacement. We tested the hypothesis that echo-guided PM repositioning using an external device can reduce MR without compromising left ventricular (LV) function. METHODS AND RESULTS: We studied 10 sheep with ischemic MR produced by circumflex ligation with inferior infarction, 6 acutely and 4 eight weeks after myocardial infarction (MI). A Dacron patch containing an inflatable balloon was placed over the PMs and adjusted under echo guidance to reverse LV remodeling and reposition the infarcted PM. 3D echo assessed mitral valve geometric changes. In 7 sheep, sonomicrometry and Millar catheters assessed changes in end-systolic and end-diastolic pressure-volume relationships, and microspheres were injected to assess coronary flow. Moderate MR after MI resolved with patch application alone (n=3) or echo-guided balloon inflation, which repositioned the infarcted PM, decreasing the PM tethering distance from 31.1+/-2.5 mm after MI to 26.8+/-1.8 with patch (P<0.01; baseline=25.5+/-1.5). LV contractility was unchanged (end-systolic slope=3.4+/-1.6 mm Hg/mL with patch versus 2.8+/-1.6 after MI). Although there was a nonsignificant trend for a mild increase in stiffness constant (0.07+/-0.05 mL(-1) versus 0.05+/-0.03 after MI, P=0.06), LV end-diastolic pressure was unchanged as MR resolved. Coronary flow to noninfarcted regions was not reduced. CONCLUSIONS: An external device that repositions the PMs can reduce ischemic MR without compromising LV function. This relatively simple technique can be applied under echo guidance in the beating heart.

Angioplasty, Balloon↗

PubMed2002

New efficient catheter-based system for myocardial gene delivery.

BACKGROUND: Manipulating gene expression in the failing heart has therapeutic promise, but until now efficient and homogeneous cardiac gene delivery has required an open-chest approach. This study examines the hypothesis that vector delivery promoted by echo contrast microbubbles will be maximized by injection of the vectors into the aortic root with brief balloon occlusion above the sinuses, while at the same time prolonging diastole and vasodilating with acetylcholine (ACh) to maximize coronary exposure. METHODS AND RESULTS: After incubation with albumin-coated perfluorocarbon microbubbles, an adenovirus encoding a reporter gene was infused into the aortic root of rats. To maximize delivery, the aortic root was transiently occluded with a balloon catheter during a brief ACh-induced asystole. Ultrasound was used to image the delivery and disrupt the microbubbles. Aortic occlusion with concomitant ACh increased myocardial gene expression for virus + microbubbles by >2.5-fold, from 925+/-165 to 2358+/-376 relative units (RU; P<0.01). This delivery system also produced substantial expression with vector alone (1473+/-549 RU). All uptakes were significant compared with 433+/-332 RU without virus. CONCLUSIONS: An adenoviral delivery system combining echo contrast with a catheter-based technique to maximize coronary perfusion increases gene delivery compared with echo contrast alone. This novel method permits efficient percutaneous gene delivery in closed-chest animals.

Acetylcholine↗

PubMed2002

Mechanistic insights into functional mitral regurgitation.

Effective valve repair in patients with mitral regurgitation (MR) demands an understanding of its mechanism. In patients with ischemic heart disease and functional MR, which doubles late mortality, normal leaflets are apically displaced. This reflects an altered balance of forces acting on the leaflets: increased tethering forces restricting closure, resulting from an altered geometry of leaflet attachments, and decreased ventricular forces acting to close the leaflets. Extensive evidence confirms a central and predominant role of tethering as the final common pathway inducing functional MR; left ventricular (LV) pressure dynamically modulates the orifice area. Because ischemic MR is a disease of the entire mitral complex, including the remodeling LV, reducing annular size alone is often ineffective. Undersizing rings attempts to compensate for tethering; new and potentially more effective strategies directly address tethering by infarct plication, papillary muscle repositioning with a localized patch, or basal chordal cutting to increase coaptational surface area without prolapse. A comprehensive understanding of the valve in its ventricular context, therefore, provides new opportunities for successful valve repair in patients.

Humans↗

PubMed2002

Effect of destructive pulse duration on the detection of myocardial perfusion in myocardial contrast echocardiography: In vitro and in vivo observations.

UNLABELLED: Myocardial perfusion is detected with contrast echocardiography by comparing a contrast-enhanced image with a baseline obtained before contrast injection (true baseline) or after myocardial bubble destruction after a high-power destructive pulse (postdestructive pulse baseline). Although it is assumed that all bubbles are destroyed by a destructive pulse insuring optimal contrast detection, this assumption has not been tested. In 18 participants we compared the videointensity (VI) differences among the contrast-enhanced image, the postdestructive pulse baseline, and the true baseline using both triggered high-mechanical index imaging and real-time imaging. VI difference was significantly greater for the true baseline with both techniques at all ventricular levels. The benefit of using a true baseline was less when the duration of the destructive pulse was increased. Similarly, we quantified VI in a flow phantom using continuous Optison (commercially available perfluoropropane-filled albumin microbubbles) (Amersham, Princeton, NJ) infusion and variable durations of destructive pulses. VI decreased with the duration of the destructive pulse and reached a plateau after a duration of 8 to 15 frames. The plateau reached after a long destructive pulse was dependent on flow rate and concentration and never reached a true baseline, unless concentration (<100 microL/L) and flow rate (<0.5 cm/s) were very low. IN CONCLUSION: (1) in clinical studies, the difference in VI between contrast-enhanced and baseline images is greater when true baseline is used; (2) the longer the destructive pulse, the closer the postdestructive pulse baseline to true baseline; and (3) this effect exists in all regions of the left ventricle.

Adult↗

PubMed2002

Determinants of maximal right ventricular function: role of septal shift.

BACKGROUND: Right heart failure can occur after orthotopic heart transplantation and can complicate implantation of left ventricular assist devices. The functional codeterminants of right ventricular function are not fully understood. We investigated the effects of left ventricular preload and afterload, systemic pressure, and the contribution of the interventricular septum to right ventricular function. METHODS AND RESULTS: In vivo studies were conducted in 12 dogs by using a highly defined, isovolumic right heart preparation. At any given arterial pressure, maximal right ventricular developed pressure was not influenced by left heart output; however, right ventricular volumes at which peak right ventricular developed pressure occurred differed significantly between the volume-loaded versus the unloaded left ventricle (P <.05). A correlation was found between peak right ventricular developed pressure and mean arterial pressure. The shift of the interventricular septum toward the left ventricle is delayed under the influence of left ventricular volume load, but the maximal interventricular septal deformation does not differ at maximal right ventricular developed pressure. There was a substantial and significant decrease in peak right ventricular developed pressure when the interventricular septum was inactivated (P <.05). CONCLUSIONS: Right ventricular function has multiple determinants, including the right ventricular free wall, the left ventricle, and the interventricular septum. Changes in right ventricular performance caused by alterations in left ventricular volume load and mean arterial pressure are mediated partially through the interventricular septum, as well as through perfusion of the right ventricular free wall; inactivation of the interventricular septum leads to a significant decrease in right ventricular function. Maintaining left ventricular developed pressure and hence the contribution of the interventricular septum to right ventricular function may be important in the management of right ventricular failure.

Animals↗

PubMed2002

Regional measurement of canine skeletal muscle blood flow by positron emission tomography with H2(15)O.

Positron emission tomography (PET) with H2(15)O was used as an in vivo, relatively noninvasive, quantitative method for measuring regional blood flow to hindlimb skeletal muscle of anesthetized dogs. A hydrooccluder positioned on the femoral artery was used to reduce flow, and high-flow states were produced by local infusion of adenosine. Three to four measurements were made in each animal. Approximately 40 mCi of H2(15)O were injected intravenously, and serial images and arterial blood samples were acquired over 2.5 min. Data analysis was performed by fitting tissue and arterial blood time-activity curves to a modified, single-compartment Kety model. The model equation was also solved on a pixel-by-pixel basis to yield maps of regional skeletal muscle blood flow. After each PET determination, flow was measured with radioactive microspheres. Results of the PET measurements demonstrated that basal flow to hindlimb skeletal muscle was 3.83 +/- 0.36 ml x min(-1) x 100 g(-1) (mean +/- SE). This value was in excellent agreement with the microsphere data, 3.73 +/- 0.32 ml x min(-1) x 100 g(-1) (P = 0.69, not significant). Adenosine infusion resulted in flows as high as 30 ml x min(-1) x 100 g(-1), and the PET and microsphere data were highly correlated over the entire range of flows (r2 = 0.98, P < 0.0001). We conclude that muscle blood flow can be accurately measured in vivo by PET with H2(15)O and that this approach offers promise for application in human studies of muscle metabolism under varying pathophysiological states.

Animals↗

PubMedDate not supplied

Autologous blood sequestration using a double venous reservoir bypass circuit and polymerized hemoglobin prime.

Cardiac surgery often necessitates transfusion of homologous blood. Hemoglobin based oxygen carrying solutions (HBOCs) transport oxygen, suggesting use in cardiopulmonary bypass. HBOC was used in a novel oxygenator double-reservoir circuit that permits acute sequestration of a portion of the autologous blood volume during bypass. Two groups of seven mongrel dogs each were studied in an experimental bypass model using global myocardial ischemia and cardioplegia protection: HBOC group, initial venous return drained to a separate reservoir and hypothermic bypass was conducted with HBOC containing perfusate in a second bypass reservoir; Control group, crystalloid prime in a conventional circuit. Hemodynamics and metabolic and hematologic parameters were measured before and 60 min after aortic clamp removal and reinfusion of sequestered autologous blood. Blood gases, base excess, hematocrit, total hemoglobin, and platelet counts were measured. In the HBOC group, metabolic acidosis did not occur, and ventricular function was preserved. Net conservation of platelets was noted at study conclusion: control 33+/-13 x 10(3) per mm3 versus HBOC 48+/-13 x 10(3), p < 0.05. HBOC based priming in a double venous reservoir system permits bypass at very low hematocrit, with preservation of cardiac function. Net conservation of the platelet mass occurs, a portion of which is not exposed to the deleterious effects of hypothermia and cardiopulmonary bypass.

Animals↗