Related Experiment Videos
d-Propranolol prevents adenosine formation associated with myocardial hypoperfusion
R D Wangler1, W P Peterson, H V Sparks
1Department of Physiology, Michigan State University, East Lansing 48824.
Insights
d-Propranolol prevents increased adenosine release from hypoperfused hearts by blocking nucleoside formation. This occurs by reducing oxygen demand, preventing oxygen supply reduction from stimulating adenosine production.
Area of Science:
- Cardiovascular Physiology
- Biochemistry
Background:
- Hypoperfusion in the heart increases adenine nucleoside release.
- d-Propranolol has been shown to eliminate this increased release.
Purpose of the Study:
- To determine if d-propranolol reduces adenosine formation or its release into the vascular compartment.
- To investigate the mechanism by which d-propranolol affects adenosine nucleoside release during hypoperfusion.
Main Methods:
- Measurement of myocardial tissue adenosine (TADO) and nucleoside release.
- Induction of hypoperfusion by reducing perfusion pressure by 50% and 75%.
- Administration of d-propranolol during hypoperfusion and assessment of its effects on coronary flow (CF), venous oxygen tension (PVO2), myocardial oxygen consumption (MVO2), and adenosine/inosine release.
Main Results:
- Hypoperfusion significantly increased TADO and adenosine/inosine release.
- d-Propranolol administration during hypoperfusion eliminated the increase in adenosine and inosine release.
- TADO remained significantly lower in hypoperfused hearts treated with d-propranolol compared to untreated hypoperfused hearts.
- d-Propranolol maintained a normal oxygen supply-to-consumption ratio despite severe hypoperfusion.
Conclusions:
- d-Propranolol blocks cardiac nucleoside formation during hypoperfusion.
- This blockade is achieved by reducing myocardial oxygen demand.
- Consequently, reduced oxygen supply does not stimulate adenosine formation in the presence of d-propranolol.
Abstract:
d-Propranolol eliminates the increased adenine nucleoside release from hypoperfused hearts [R. D. Wangler, D. F. DeWitt, and H. V. Sparks, Am. J. Physiol. 247 (Heart Circ. Physiol. 16): H330-H336, 1984]. To determine whether d-propranolol reduces adenosine formation or adenosine release into the vascular compartment, we measured myocardial tissue adenosine (TADO). Decreased formation would lower TADO, whereas decreased release would elevate TADO. Reduction of perfusion pressure by 50% reduced coronary flow (CF), venous oxygen tension (PVO2), and myocardial oxygen consumption (MVO2) by approximately 40, 25, and 35%, respectively. Total adenosine and inosine released during 30 min of hypoperfusion increased 10- and 5-fold, respectively. Also, TADO increased from 2.68 +/- 0.37 to 5.17 +/- 0.67 nmol/g (P less than 0.05). In the presence of d-propranolol, the same reduction in perfusion pressure caused a similar decrease in CF and MVO2. d-Propranolol eliminated the release of adenosine and inosine associated with hypoperfusion. TADO after 30 min of hypoperfusion plus d-propranolol was not significantly increased (3.27 +/- 0.40 nmol/g) and was significantly less than hypoperfused hearts. When severe hypoperfusion was created by reducing perfusion pressure 75%, adenosine release still did not increase if d-propranolol was present. When adenosine release was plotted as a function of oxygen supply-consumption, they were related in a hyperbolic fashion. Despite the severity of hypoperfusion, in the presence of d-propranolol the supply-to-consumption ratio was similar to that of the control perfusion group (no drug). We conclude that d-propranolol blocks nucleoside formation during hypoperfusion by reducing oxygen demand such that a reduction of oxygen supply no longer stimulates adenosine formation.