1.Assessment Coronary Flow Reserve And The Effects Of Hypertension And Hypoxia By Real-time Myocardial Contrast Echocardiography 2.A New Method Of Inducing Heart Failure Model In Mouse

Background:Time-intensity curves derived from microbubble destruction/refilling sequences recorded from myocardial contrast echo(MCE) can provide parameters which correlate with coronary blood flow.The response of these parameters to adenosine(ADN) vasodilation correlates with coronary flow reserve (CFR) measured by microsphere techniques.However,no data exist regarding the effect of physiological variables such as blood pressure and oxygen tension upon the determination of CFR by MCE.Methods:Studies were performed in 18 closed chest swine.Low-energy, real-time MCE was performed in short axis papillary muscle view while infusing BR1(Sonovue,Bracco) at 30 ml/hr.High-energy FLASH frames destroyed bubbles every 15 cardiac cycles,and time-intensity curves derived from refilling were fitted to an exponential function as y=A(1-e^-bt) +C from which the rate of signal rise(b) was obtained.CFR was calculated as the ratio of b values prior to and after adenosine infusion,and was obtained during control(CON) and after increasing BP with phenylephrine in 9 out of the 18 pigs,and after inducing hypoxia by breathing nitrogen in another 9 pigs out of the 18 pigs.CFR was independently determined by fluorescent microspheres.Results:Adenosine produced a similar increase of CFR by MCE and microspheres(2.5 vs 3.1 respectively) during CON.Phenylephrine increased the mean BP from 129/107 to 196/153mmHg(P＜0.001) and changed heart rate from 114 to 124(P＞0.05).Phenylephrine increased resting and decreased post adenosine values of b(0.71 and 0.92 respectively),producing a marked reduction in CFR which was similar to that measured by microspheres(1.5 and 1.8 respectively,both P＜0.05). Nitrogen inhalation decreased the mean PaO₂ from 120.6 to 51.8mmHg,(P＜0.001), without a change of heart rate(114 to 116 beats/min).The decrease of PaO₂ resulted in slightly increased resting values for both b(0.46 to 0.51) and MBF(1.39 to 1.72), both nonsignificant,and slightly decreased values after adenosine:1.05 to 0.82 for b and 4.30 to 3.93 for MBF,both P＞0.05.Thus,CFR decreased with hypoxia:to 1.42 by b parameter,P＜0.05,and 2.5 by MBF(P＞0.05).Conclusions::Trans-vein real-time MCE is a ideal method to assess coronary flow reserve.It is fissiable,repeatable.Phenylepherine induced hypertension and hypoxia reduces quantitative parameters of CFR derived from destroy/refill sequences by MCE.The influence of these variables must be taken into account when employing MCE to assess coronary flow reserve. Purpose:A standardized heart failure model was induced by cryo-injury.Methods:Cryo-injury was produced in anesthetized C57BL/6 mice via 10s of direct contact on the LV anterior free wall with a 4 mm Brymill liquid nitrogen chilled probe.MI was induced by coronary artery ligation. Echocardiograms of fractional shortening and LV end diastolic and systolic dimensions were made before(baseline),35d and 70d post-injury.Also in-situ contractility and ejection fraction were assessed at 70d post-injury, and triphenyltetrazolium chloride(TTC) stain was used to delineate infarction.Gs protein and adenylyl cyclase content were test in by Western method in cryo-injury mouse and compared to normal heart.Results:The myocardial cryo-injury scar size determined by TTC stain was profoundly large(51±1%,n=9).Echocardiographic and in situ parameters revealed a highly enlarged and dysfunctional heart.Both Gs protein and adenlyly cyclase were unchanged in the cryo-ingery group.Conclusion:cryo-injury created a more standardized mouse heart failure model and higher survival rate than coronary ligation did.Both Gs protein and adenlyly cyclase were unchanged when heart failure was developed.