What is the clinical evidence from this study?

Study design: Other. Population: Coronary autoregulation. Intervention: N omega-nitro-L-arginine methyl ester (L-NAME) vs. Control conditions. Primary outcome: Critical pressure at which myocardial ischemia began (lower autoregulatory break point) (p=<.001).

August 1, 1993Open Access

Modulation of coronary autoregulatory responses by nitric oxide. Evidence for flow-dependent resistance adjustments in conscious dogs.

Q: What are the key findings of this study?

In conscious dogs, L-NAME increased the critical coronary pressure at which myocardial ischemia began from 45 +/- 3 mm Hg to 61 +/- 2 mm Hg (P < .001).

Key Result

In conscious dogs, L-NAME increased the critical coronary pressure at which myocardial ischemia began from 45 +/- 3 mm Hg to 61 +/- 2 mm Hg (P < .001).

PICO

Population

Unanesthetized dogs undergoing inhibition of nitric oxide synthesis with L-NAME to assess coronary autoregulatory responses.

Intervention / Comparator

N omega-nitro-L-arginine methyl ester (L-NAME) vs Control conditions (10 mg/kg)

Primary Outcome

Critical pressure at which myocardial ischemia began (lower autoregulatory break point), p=<.001

Main Result

Absolute Event Rate: 61% vs 45%

p-value: p=<.001

Abstract

The present study tested the hypothesis that nitric oxide production in coronary resistance vessels is an important mechanism affecting the regulation of myocardial perfusion in unanesthetized dogs. We inhibited nitric oxide synthesis with the arginine analogue N omega-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg) and maintained the compressive determinants of myocardial blood flow constant by ventricular pacing. L-NAME did not affect resting coronary blood flow and reduced the receptor-mediated increase in flow to intracoronary acetylcholine (100 micrograms/min IC) from 143 +/- 20% (mean +/- SEM) under control conditions to 31 +/- 10% after L-NAME (P < .001). Coronary autoregulatory relations were determined as steady-state coronary pressure was reduced by inflating a hydraulic occluder. Initial resistance adjustments over the autoregulatory plateau were not affected by L-NAME. Closed-loop autoregulatory gain was 0.84 +/- 0.09 under control conditions versus 0.78 +/- 0.07 after L-NAME (P = NS). As coronary pressure was reduced further, however, the critical pressure at which myocardial ischemia began (lower autoregulatory break point) increased from 45 +/- 3 mm Hg under control conditions to 61 +/- 2 mm Hg (P < .001) after L-NAME. In addition, the slope of the coronary pressure-flow relation below the autoregulatory break point was reduced (1.0 +/- 0.2 versus 0.58 +/- 0.09 mL.min-1.mm Hg-1 after L-NAME, P < .05), reflecting a reduction in the maximal conductance recruitable during ischemia. In concert with the effects of L-NAME on autoregulatory responses during ischemia, peak reactive hyperemic flow to a 30-second coronary occlusion was also reduced (from 200 +/- 22 to 166 +/- 24 mL/min after L-NAME, P < .01).(ABSTRACT TRUNCATED AT 250 WORDS)