Preoxygenated hemoglobin-based oxygen carrier HBOC-201 annihilates myocardial ischemia during brief coronary artery occlusion in pigs

2010 ◽  
Vol 298 (3) ◽  
pp. H1103-H1113 ◽  
Author(s):  
Maaike te Lintel Hekkert ◽  
Gregory P. Dubé ◽  
Evelyn Regar ◽  
Martine de Boer ◽  
Pascal Vranckx ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Stroke Volume ◽  
Reactive Hyperemia ◽  
Balloon Catheter ◽  
Coronary Artery Occlusion ◽  
Artery Occlusion ◽  
Left Ventricular ◽  
Lv Function ◽  
Dependent Manner ◽  
Myocardial Oxygenation

Because of their ability to perfuse remote regions and deliver oxygen, hemoglobin-based oxygen carriers (HBOCs) may be considered in the treatment of several ischemic conditions such as acute coronary syndromes or high-risk percutaneous intervention. Here we studied the effects of intracoronary infusion of ex vivo preoxygenated HBOC-201 during brief total coronary artery occlusion (CAOs) on myocardial oxygenation and left ventricular (LV) function in a large animal model and investigated the influence of HBOC-201 temperature and infusion rate on these effects. Thirteen open-chest anesthetized swine were instrumented for measurement of global and regional LV function and metabolism. CAOs were induced by inflating an intracoronary balloon catheter; preoxygenated HBOC-201 (12 g/dL) was infused distally through the central lumen of the balloon catheter. Animals underwent consecutive 3-min CAOs interspersed by 30 min of reperfusion, accompanied by different HBOC-201 infusion rates (0, 15, 23, 30, 40, and 50 ml/min) and/or two infusion temperatures (18°C or 37°C) in random order. CAO elicited immediate loss of systolic shortening (SS) in the ischemic region (19 ± 1% at baseline vs. −3 ± 2% at end of CAO), resulting in decreases in maximum rate of rise in LV pressure (15 ± 5%) and stroke volume (12 ± 4%; all P < 0.05). Balloon deflation resulted in marked coronary reactive hyperemia (to 472 ± 74% of baseline), increases in coronary venous concentrations of adenosine + inosine (to 218 ± 26% of baseline; both P < 0.05) and rapid restoration of SS toward baseline. HBOC-201 ameliorated the CAO-induced changes in SS, stroke volume, reactive hyperemia, and coronary venous adenosine + inosine. The effects were temperature and flow dependent with full preservation of SS at 50 ml/min HBOC-201 of 37°C. In conclusion, intracoronary preoxygenated HBOC-201 preserved myocardial oxygenation and LV function in swine during CAO in a dose- and temperature-dependent manner. In our study setting, preoxygenated HBOC-201 can match the oxygen delivery role of endogenous blood in the heart on an almost equivalent-volume basis.

Myocardial infarction with and without reperfusion in sheep: early cardiac and neurohumoral changes

2000 ◽  
Vol 98 (6) ◽  
pp. 703-711 ◽  
Author(s):  
Christopher J. CHARLES ◽  
John M. ELLIOTT ◽  
M. Gary NICHOLLS ◽  
Miriam T. RADEMAKER ◽  
Mark RICHARDS
Keyword(s):  
Myocardial Infarction ◽  
Coronary Artery ◽  
Ejection Fraction ◽  
Troponin T ◽  
Coronary Artery Occlusion ◽  
Artery Occlusion ◽  
Left Ventricular ◽  
Lv Function ◽  
Large Animal ◽  
Lv Dysfunction

There are few stable and reproducible large-animal models of chronic heart failure produced by ischaemic damage to the myocardium. Here we characterize a novel method of inducing myocardial damage in closed-chest sheep by catheter delivery of thrombogenic coils, and compare this with a newly described open-artery model of cardiac injury in sheep. Sham controls were compared with animals subjected to (a) 90 min of coronary artery occlusion/reperfusion by PTCA (percutaneous transluminal coronary angioplasty) balloon, and (b) permanent coronary artery occlusion induced by catheter delivery of thrombogenic coils (seven sheep/group). Both balloon occlusion/reperfusion and permanent coil occlusion resulted in well-defined anteroapical infarcts, as documented by ECG changes, significant rises in creatine kinase (both groups P < 0.001) and troponin-T (both groups P < 0.05), and post-mortem examination. Washout of enzymes was much more rapid in the reperfused group (P < 0.01). Infarction resulted in significant reductions in left ventricular (LV) ejection fraction (both groups P < 0.01) and regional wall abnormalities. Ejection fraction 7 days post-coil (21.3±4.2%) was significantly lower (P < 0.01) than that 7 days post-balloon (38.8±4.5%). Coil-induced infarction was associated with acutely reduced arterial pressure (P < 0.05), and increases in heart rate (P < 0.05), atrial pressures (P < 0.05), plasma brain natriuretic peptide levels (P < 0.05) and adrenaline levels (P < 0.05). Rises seen in plasma endothelin levels in sham controls were blunted in the coil group (P < 0.001). Haemodynamic changes were less marked in the balloon group. In conclusion, restriction of coronary artery occlusion to 90 min results in infarction, but less LV dysfunction with reduced early remodelling, compared with permanent occlusion. Acute changes in biochemical markers, haemodynamics, neurohormones and LV function confirm that these are excellent models of open- and closed-artery myocardial infarction leading to asymptomatic LV dysfunction.

A new thermal sensor for surface-based measurement of local myocardial perfusion

1983 ◽  
Vol 244 (3) ◽  
pp. H449-H453
Author(s):  
F. S. Castellana ◽  
R. B. Case ◽  
R. Skalak ◽  
J. M. Cho
Keyword(s):  
Blood Flow ◽  
Coronary Artery ◽  
Reactive Hyperemia ◽  
Coronary Artery Occlusion ◽  
Artery Occlusion ◽  
Tissue Blood Flow ◽  
Thermal Sensor ◽  
Epicardial Surface ◽  
Continuous Surface ◽  
Flow Changes

The transient response of a new thermal sensor for continuous surface-based measurement of local tissue blood flow was evaluated in the beating dog heart. The sensor is 2.5 mm square, tests on the heart, and responds to flow changes only within a region of tissue 3-4 mm below its location on the epicardial surface. Initial studies demonstrate excellent sensitivity, good frequency response with a time constant of the order of 10-11 s, and an ability to continuously monitor changes in local myocardial blood flow during a variety of well-understood interventions, including coronary artery occlusion, reactive hyperemia, and intravenous administration of nitroglycerin and dipyridamole.

Effect of exercise on coronary pressure-flow relationship in hypertrophied left ventricle

1995 ◽  
Vol 269 (1) ◽  
pp. H271-H281 ◽  
Author(s):  
D. J. Duncker ◽  
J. Zhang ◽  
T. J. Pavek ◽  
M. J. Crampton ◽  
R. J. Bache
Keyword(s):  
Coronary Artery ◽  
Myocardial Perfusion ◽  
Diastolic Pressure ◽  
Coronary Artery Occlusion ◽  
Artery Occlusion ◽  
Left Ventricular ◽  
Back Pressure ◽  
Pressure Flow ◽  
Pronounced Increase ◽  
Coronary Pressure

Left ventricular (LV) hypertrophy (LVH) secondary to chronic pressure overload is associated with increased susceptibility to myocardial hypoperfusion and ischemia during exercise. The present study was performed to determine whether exercise causes alterations in minimum coronary resistance or effective back pressure [coronary pressure at zero flow (Pzf)] that limit maximum myocardial perfusion in the hypertrophied heart. Ascending aortic banding in 7 dogs increased the LV weight-to-body weight ratio to 7.7 +/- 0.3 g/kg compared with 4.6 +/- 0.2 g/kg in 11 normal dogs (P < 0.01). Maximum coronary vasodilation was produced by intracoronary infusion of adenosine. Under resting conditions, the slope of the pressure-flow relationship (conductance) was significantly lower in the LVH animals than in the normal dogs (7.2 +/- 0.8 vs. 11.9 +/- 0.8 x 10(-2) ml.min-1.g-1.mmHg-1; P < 0.01); the slope correlated with the degree of hypertrophy r = 0.74; P < 0.001). The Pzf measured during total coronary artery occlusion (Pzf,measured) was significantly elevated in LVH compared with normal dogs (25.6 +/- 2.2 vs. 13.0 +/- 1.2 mmHg; P < 0.01); Pzf,measured was positively correlated (r = 0.78, P < 0.0005) with LV end-diastolic pressure measured during total coronary artery occlusion (9.0 +/- 1.1 mmHg in normal dogs and 22.2 +/- 3.2 mmHg in LVH dogs; P < 0.01). Graded treadmill exercise to maximum heart rates of 210 +/- 9 and 201 +/- 8 beats/min in normal and LVH animals, respectively, caused similar decreases in the slope of the pressure-flow relationship in LVH (from 7.7 +/- 0.9 to 6.1 +/- 0.8 x 10(-2) ml.min-1.g-1.mmHg-1; P < 0.01) and normal dogs (from 11.9 +/- 0.8 to 10.0 +/- 0.7 x 10(-2) ml.min-1.g-1.mmHg-1; P < 0.01). However, exercise-induced increases in Pzf,measured were significantly greater in the LVH animals (from 25.6 +/- 2.2 to 40.8 +/- 2.1 mmHg; P < 0.01) than in normal animals (from 13.0 +/- 1.2 to 24 +/- 2.1 mmHg; P < 0.01) (P < 0.01 LVH vs. normal). The greater increase in Pzf paralleled a more pronounced increase in LV end-diastolic pressure in the LVH dogs from 22.2 +/- 3.2 to 39.1 +/- 2.7 mmHg) than in normal dogs from 9.0 +/- 1.1 to 14.2 +/- 2.0 mmHg). The results suggest that exaggerated increases in filling pressure during exercise in the hypertrophied left ventricles contributed to impairment of myocardial perfusion during exercise by augmenting the back pressure, which opposes coronary flow.(ABSTRACT TRUNCATED AT 400 WORDS)

Long-Term Effects of Growth Hormone on Infarct Size and Left Ventricular Function in Sheep With Coronary Artery Occlusion

2010 ◽  
Vol 55 (3) ◽  
pp. 255-261
Author(s):  
Fernanda D Olea ◽  
Andrea De Lorenzi ◽  
Claudia Cortés ◽  
Patricia Cabeza Meckert ◽  
Oscar Cendoya ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Coronary Artery ◽  
Left Ventricular Function ◽  
Infarct Size ◽  
Ventricular Function ◽  
Coronary Artery Occlusion ◽  
Artery Occlusion ◽  
Left Ventricular ◽  
Long Term Effects
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