Myocardial oxygen tension and capillary density in the isolated perfused rat heart during pharmacological intervention.
Oxygen is essential for normal cardiac function and plays an important role in cardiac regulation. Electron paramagnetic resonance (EPR) oximetry appears to have some significant advantages for measuring oxygen tension (pO2) in the beating heart. This study presents the serial measurement of myocardial pO2 by EPR oximetry in the isolated crystalloid perfused heart during treatment with different cardioactive drugs: dobutamine, metoprolol, verapamil, vasopressin, and N omega-Nitro-L-Arginine Methyl Ester (L-NAME). Baseline myocardial pO2 was 176 +/- 14 mmHg (mean +/- S.E.). Myocardial capillary density in the intact contracting heart was calculated to be 2300 +/- 100 mm-2, using local myocardial pO2 and a cylindrical model for oxygen diffusion in tissue. Each drug had characteristic effects on myocardial pO2, myocardial oxygen consumption (MVO2), and capillary density. Metoprolol and verapamil increased myocardial pO2 by 51% and 18%, respectively, dobutamine decreased myocardial pO2 by 84% while vasopressin and L-NAME had no significant effect on myocardial pO2. Metoprolol and verpamil decreased MVO2 by 9% and 56%, respectively, while dobutamine increased MVO2 by 59%. A quantitative comparison of effects on the capillary bed based on changes in myocardial pO2 and MVO2 was made. Metoprolol and verapamil had opposite effects on the capillary bed. Verapamil decreased myocardial capillary density by 39%, while capillary density increased by 10% (n.s.) with metoprolol. Data following perfusion without drug is also presented. We conclude that: 1) The application of EPR oximetry with LiPc provides dynamic evaluation of local myocardial pO2 in the contracting heart. 2) Using a cylindrical model of oxygen delivery and diffusion in tissue, these data may be used to describe the changes of capillary density during pharmacological interventions.
Grinberg
O Y
OY
Department of Radiology, Dartmouth-Hitchcock Medical Center, Hanover, New Hampshire 03755, USA.
Grinberg
S A
SA
Friedman
B J
BJ
Swartz
H M
HM
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002196:Capillaries / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism; D004280:Dobutamine / Q000494:pharmacology; D004578:Electron Spin Resonance Spectroscopy; D006321:Heart / Q000187:drug effects; D066298:In Vitro Techniques; D007211:Indoles; D008297:Male; D008790:Metoprolol / Q000494:pharmacology; D009206:Myocardium / Q000378:metabolism*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors; D009942:Organometallic Compounds; D010100:Oxygen / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D013113:Spin Labels; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014667:Vasopressins / Q000494:pharmacology; D016277:Ventricular Function, Left / Q000187:drug effects; D014700:Verapamil / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D002121:Calcium Channel Blockers; D007211:Indoles; D009942:Organometallic Compounds; D013113:Spin Labels; D014662:Vasoconstrictor Agents; D014667:Vasopressins; C081756:lithium phthalocyanine; D009569:Nitric Oxide; D004280:Dobutamine; D014700:Verapamil; D008790:Metoprolol; D010100:Oxygen; D019331:NG-Nitroarginine Methyl Ester