Effects of red wine and vodka on collateral-dependent perfusion and cardiovascular function in hypercholesterolemic swine

Abstract

Background: Moderate consumption of alcohol, particularly red wine, has been shown to decrease cardiac risk. We used a hypercholesterolemic swine model of chronic ischemia to examine the effects of 2 alcoholic beverages on the heart.

Methods and results: Yorkshire swine fed a high-cholesterol diet underwent left circumflex ameroid constrictor placement to induce chronic ischemia at 8 weeks of age. One group (HCC, n=9) continued on the diet alone, the second (HCW, n=8) was supplemented with red wine (pinot noir, 12.5% alcohol, 375 mL daily), and the third (HCV, n=9) was supplemented with vodka (40% alcohol, 112 mL daily). After 7 weeks, cardiac function was measured, and ischemic myocardium was harvested for analysis of perfusion, myocardial fibrosis, vessel function, protein expression, oxidative stress, and capillary density. Platelet function was measured by aggregometry. Perfusion to the ischemic territory as measured by microsphere injection was significantly increased in both HCW and HCV compared with HCC at rest, but in only the HCW group under ventricular pacing. Microvessel relaxation response to adenosine 5'-diphosphate was improved in the HCW group alone as was regional contractility in the ischemic territory, although myocardial fibrosis was decreased in both HCW and HCV. Expression of proangiogenic proteins phospho-endothelial nitric oxide synthase and vascular endothelial growth factor was increased in both HCW and HCV, whereas phospho-mammalian target of rapamycin was increased only in the HCV group. Expression of Sirt-1 and downstream antioxidant phospho-FoxO1 was increased only in the HCW group. Protein oxidative stress was decreased in the HCW group alone, whereas capillary density was increased only in the HCV group. There was no significant difference in platelet function between groups.

Conclusion: Moderate consumption of red wine and vodka may reduce cardiovascular risk by improving collateral-dependent perfusion through different mechanisms. Red wine may offer increased cardioprotection related to its antioxidant properties.

Figure 1. Serum chemistries

Whole blood drawn at the terminal procedure was analyzed for total and HDL cholesterol, and the LDL:HDL ratio was calculated. Blood was also drawn one hour postprandially for quantification of blood alcohol levels. There was no difference in total cholesterol or LDL:HDL ratio between groups (A,C), but HDL cholesterol was significantly increased in HCW and HCV compared to HCC (B). Blood alcohol levels were similarly elevated in both HCW and HCV swine (D). *p<0.05, †p<0.01.

Figure 2. Myocardial function

Developed left ventricular pressure (DLVP) and LV contractility (+dP/dt) were measured using a pressure catheter inserted directly into the LV. There was no significant difference in DLVP or +dP/dt between groups (A,B). Vertical segmental shortening was decreased in the HCV group compared to both other groups (C), while horizontal segmental shortening was improved in the HCW group compared to both other groups. *p<0.05, ‡p<0.001.

Figure 3. Myocardial perfusion

Perfusion in the AAR was measured by microsphere injection at rest and under ventricular pacing to 160 bpm. At rest, both wine and vodka administration improved perfusion to the ischemic territory (A). However, under ventricular pacing, myocardial perfusion was improved only in the HCW group (B). *p<0.05, †p<0.01.

Figure 4. Microvessel function and myocardial fibrosis

Microvessel relaxation responses to endothelium-dependent ADP and endothelium-independent SNP were measured in coronary arterioles from the AAR. A significant improvement in endothelium-dependent vasodilation was seen in the HCW group compared to both HCC and HCV (A). There was no difference between groups in endothelium-independent vasodilation (B). Myocardial fibrosis as measured by trichrome staining was significantly higher in the HCC group than in both other groups. Shown are representative trichrome stained myocardial sections from the three groups, with myocardium staining red and intervening connective tissue staining blue (C). *p<0.05, †p<0.01, ‡p<0.001.

Figure 5. Immunoblotting

Expression of proangiogenic proteins phospho-eNOS, VEGF, and phospho-mTOR, antioxidant proteins Sirt-1 and phospho-FOXO1, and total protein oxidation in the AAR were measured by immunoblotting. Both alcoholic beverages increased the expression of phospho-eNOS and VEGF (A,B), while only red wine significantly increased the expression of Sirt-1 and phospho-FOXO1 (C,D), though Sirt-1 tended to be elevated in the HCV group as well. Phospho-mTOR was only upregulated in the HCV group (E). Protein oxidative stress was significantly reduced in the HCW group compared to both other groups (F). *p<0.05, †p<0.01, ‡p<0.001.