What is the clinical evidence from this study?

Study design: Other. Population: Alloxan-induced diabetes. Intervention: Alloxan-induced diabetes vs. Pre-diabetes (control). Primary outcome: Increase in coronary blood flow in response to 5 micrograms/kg of veratrine (p=< 0.05).

What question did this study set out to answer?

Investigate how alloxan-induced diabetes alters nitric oxide production and the regulation of coronary blood flow in conscious dogs.

July 1, 1999AJP Heart and Circulatory Physiology

Reduced coronary NO production in conscious dogs after the development of alloxan-induced diabetes

Q: What are the key findings of this study?

The development of alloxan-induced diabetes in conscious dogs significantly reduced the coronary blood flow increase in response to veratrine from 57% to 32% (P<0.05).

Q: What question did this study set out to answer?

Investigate how alloxan-induced diabetes alters nitric oxide production and the regulation of coronary blood flow in conscious dogs.

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Key result

The development of alloxan-induced diabetes in conscious dogs significantly reduced the coronary blood flow increase in response to veratrine from 57% to 32% (P<0.05).

Population

Mongrel dogs with alloxan-induced diabetes (40-60 mg/kg iv)

Comparison

Alloxan-induced diabetes vs Pre-diabetic state (control)

Design

Preclinical

Follow-up

4-5 weeks

Authors

GZGong ZhaoGilead Sciences (Spain)XZXiao–Ping ZhangUniversity Town of Shenzhen CSCarolyn J. SmithUniversity of California, Riverside

Discussion

Member takes

Implication

Diabetes impairs NO-dependent coronary vasodilation in dogs; hypothesis-generating for human endothelial dysfunction and should not change practice.

Key Points

Investigate how alloxan-induced diabetes alters nitric oxide production and the regulation of coronary blood flow in conscious dogs.
Chronically instrumented conscious mongrel dogs with paced heart rates (150 beats/min) to record systemic hemodynamics and coronary blood flow.
Induced diabetes with intravenous alloxan (40–60 mg/kg; blood glucose 384 ± 18 mg/dl at 4–5 weeks) and measured vascular responses to veratrine, acetylcholine, and adenosine.
Quantified microvascular nitrite production alongside aortic endothelial nitric oxide synthase mRNA and protein levels via Northern and Western blotting.
Veratrine (5 µg/kg) increased coronary blood flow by 32 ± 2% after diabetes compared to 57 ± 7% at baseline (P < 0.05).
Coronary vasodilation induced by acetylcholine and adenosine was significantly reduced, with diminished microvascular nitrite production in response to acetylcholine and bradykinin.
Aortic endothelial constitutive nitric oxide synthase protein decreased by 66% following diabetes, despite a twofold increase in its mRNA.

Structured PICO

Population

Mongrel dogs evaluated before and 4-5 weeks after the development of alloxan-induced diabetes.

Exposure

Alloxan-induced diabetes (evaluated 4-5 weeks post-injection)

Comparator

Pre-diabetic state (control)

Outcome

Coronary blood flow (CBF) response to veratrine, ACh, and adenosinesurrogate

Main Result

Absolute Event Rate: 32% vs 57%

p-value: p=< 0.05

Alloxan-induced diabetes in dogs impairs NO-dependent coronary vasodilation, likely due to decreased NO release from the endothelium.

Cite This Study

Zhao et al. (1999) studied Alloxan-induced diabetes. Alloxan-induced diabetes vs. Pre-diabetes (control) was evaluated on Increase in coronary blood flow in response to 5 micrograms/kg of veratrine (p=< 0.05). The development of alloxan-induced diabetes in conscious dogs significantly reduced the coronary blood flow increase in response to veratrine from 57% to 32% (P<0.05).

synapsesocial.com/papers/6a732bb3ca0cfc242ec235e8 https://doi.org/10.1152/ajpheart.1999.277.1.h268

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Implication

Diabetes impairs NO-dependent coronary vasodilation in dogs; hypothesis-generating for human endothelial dysfunction and should not change practice.

Reduced coronary NO production in conscious dogs after the development of alloxan-induced diabetes

Discussion

Member takes

Implication

Key Points

Structured PICO

Main Result

Cite This Study

Reduced coronary NO production in conscious dogs after the development of alloxan-induced diabetes

Discussion

Member takes

Implication

Key Points

Structured PICO

Main Result

Cite This Study

Also Consider

Also Consider