Publications

PURPOSE: We investigated whether bilateral, lower limb remote ischemic preconditioning (RIPC) improved long-term survival using a rat model of hemorrhagic shock/resuscitation.

METHODS: Rats were anesthetized, intubated and ventilated, and randomly assigned to RIPC, induced by inflating bilateral pressure cuffs around the femoral arteries to 200 mmHg for 5 min, followed by 5-min release of the cuffs (repeated for 4 cycles), or control group (cuffs were inflated to 30 mmHg). Hemorrhagic shock was induced by withdrawing blood to a fixed mean blood pressure of 30 mmHg for 30 min, followed by 30 min of resuscitation with shed blood. Rats remained anesthetized for 1 h during which hemodynamics were monitored then they were allowed to survive for 6 weeks.

RESULTS: The percentage of estimated total blood volume withdrawn to maintain a level of 30 mmHg was similar in both groups. RIPC significantly increased survival at 6 weeks: 5 of 27 (19%) rats in the control group and 13 of 26 (50%; p = 0.02) rats in the RIPC group survived. Blood pressure was higher in the RIPC group. The diastolic internal dimension of the left ventricle, an indicator of circulating intravascular blood volume, was significantly larger in the RIPC group at 1 h after initiation of resuscitation compared to the control group (p = 0.04). Left ventricular function assessed by fractional shortening was comparable in both groups at 1 h after initiation of resuscitation. Blood urea nitrogen (BUN) was within normal range in the RIPC group (17.3 ± 1.2 mg/dl) but elevated in the control group (22.0 ± 1.7 mg/dl) at 48 h after shock.

CONCLUSIONS: RIPC significantly improved short-term survival in rats that were subjected to hemorrhagic shock, and this benefit was maintained long term. RIPC led to greater circulating intravascular blood volume in the early phase of resuscitation and improved BUN.

Heart failure is a major cause of morbidity and mortality around the world, and myocardial infarction is its leading cause. Myocardial infarction destroys viable myocardium, and this dead tissue is replaced by a non-contractile scar that results in impaired cardiac function and a significantly increased likelihood of the patient developing heart failure. Limiting infarct scar size has been the target of pre-clinical and clinical investigations for decades. However, beyond reperfusion, few therapies have translated into the clinic that limit its formation. New approaches are needed. This review will focus on new clinical and pre-clinical data demonstrating that acute ventricular unloading prior to reperfusion by means of percutaneous left ventricular support devices reduces ischemia-reperfusion injury and limits infarct scar size. Emphasis will be given to summarizing our current mechanistic understanding of this new therapeutic approach to treating myocardial infarction.

Erectile dysfunction (ED), which worldwide is likely to affect in excess of 300 million men by 2025, is often either untreated or insufficiently treated. It can be a prelude to other serious illnesses and may be a cause or consequence of depression in affected individuals. Among men younger than 60 years of age, ED can be a robust early-stage indicator of vascular disease and type 2 diabetes. Untreated or inadequately treated ED can also be a sign of poor communication between health professionals and service users of all ages. Improved treatment of ED could cost-effectively prevent premature deaths and avoidable morbidity. The extension of community pharmacy‒based health care would enable more men living with ED to safely access effective medications, along with appropriate diagnostic services and support for beneficial lifestyle changes such as smoking cessation in conveniently accessible settings. The task of introducing improved methods of affordably addressing problems linked to ED exemplifies the strategic challenges now facing health care systems globally. Promoting professionally supported self-care in pharmacies has the potential to meet the needs of aging populations in progressively more effective ways.

Acute myocardial infarction (MI) is still a large source of morbidity and mortality worldwide. Although early reperfusion therapy has been prioritized in the modern era of percutaneous coronary intervention and thrombolysis, attempts at incremental improvements in clinical outcomes by reducing MI size have not been successful so far. Herein, we review the studies that have evaluated immediate-onset antiplatelet therapy as attempts to improve meaningful clinical outcomes in ST-segment elevation MI (STEMI). Unfortunately, many of the adjunctive pharmacotherapies have proven to be disappointing. Recent studies performed in the background of routine oral administration of P2Y12 adenosine receptor inhibitors, which may take several hours to take full effect, and aspirin have largely shown no improvement in outcomes, despite an earlier onset of antiplatelet activity of the investigative agents. Further progress in improving outcomes during STEMI may depend on exploring therapeutics that modulate the pathophysiology of microvascular damage during ischemia-reperfusion injury, a phenomenon whose effects evolve over hours to days. We speculate that the dynamic nature of the no-reflow phenomenon may be an explanation for these disappointing results with the intravenous antiplatelet agents. We hope that appreciation for what has not worked in this domain may direct future research efforts to focus on novel pathways. Myocardial ischemia and reperfusion injury are very much still a lingering issue. Despite significant improvements in door-to-balloon times, rates of in-hospital mortality for STEMI remain unchanged. Outcomes following successfully reperfused STEMI are likely determined by the initial size of myocardial necrosis (ie, cardiomyocyte death during the period of ongoing ischemia), patency of the infarct-related epicardial coronary artery, possible reperfusion injury, the microvascular no-reflow phenomenon, and adverse remodeling after infarction.

AIMS: The purpose of the study was to determine whether late therapeutic hypothermia (LTH), administered after reperfusion, could prevent adverse left ventricular (LV) remodeling and improve cardiac function in the rat myocardial ischemia/reperfusion model.

MAIN METHODS: Rats were randomized to normothermia (n = 10) or LTH (initiated at 1 min after coronary artery reperfusion, n = 10) and subjected to 30 min of coronary occlusion followed by 6 weeks of reperfusion. Hypothermia was induced by pumping cold saline over the anterior surface of the LV until the temperature cooled to <32 °C. In the normothermic group, the heart was bathed in saline at 38 °C.

KEY FINDINGS: After 6 weeks of recovery, fractional shortening of the LV was comparable in the LTH (20.2 ± 0.6%) and normothermic group (20.0 ± 2.1%; p = 0.918). Postmortem LV volume (0.47 ± 0.04 ml in LTH and 0.44 ± 0.05 ml in normothermic group) and lung wet/dry weight ratio were similar in both groups. There were no significant differences in scar size, scar thickness, infarct expansion index, LV cavity or transmurality (%) between groups. This data contrasts with our previous study showing that hypothermia administered during the ischemic phase significantly reduced the scar size; decreased LV cavity, infarct expansion index and transmurality (%), and improved the scar thickness.

SIGNIFICANCE: LTH did not prevent adverse LV remodeling nor improve cardiac function in the rat myocardial ischemia/reperfusion model. To have a long term benefit on remodeling, hypothermia must be administered during the ischemic phase and not just the reperfusion phase.

There is evidence that certain stressors can trigger cardiovascular events. Several studies have now demonstrated an increase in major adverse cardiac events associated with natural disasters such as an earthquake. The purpose of this paper is to review the literature on earthquakes and cardiovascular events. Reports from 13 major quakes were reported. Earthquakes have been associated with a number of cardiac events including sudden cardiac death, fatal myocardial infarction (MI), myocardial infarction, stress cardiomyopathy, heart failure, stroke, arrhythmias, hypertension and pulmonary embolism. Most reports were associated with earthquakes of magnitude 6.0 or greater. Cardiac events were reported within hours of the quakes. In some reports there was a sharp spike in cardiac events followed by a decrease; but in other quakes the increases in cardiac events lasted weeks, months and even years. There often was an association between the cardiac events and amount of personal property loss. The Great East Japan Earthquake was an unusual event in that it was associated with a major tsunami and cardiac events appeared worse in inundated areas due to flooding. Some but not all reports suggested more MIs associated with early morning earthquakes that woke up the population. Hospitals in earthquake-prone areas should consider developing plans for handling increases in myocardial infarctions and other cardiac events that are associated with earthquakes.

Heart attacks kill more Americans than all cancers combined. Fatal heart attack victims have no symptoms until minutes before they die, hence early detection of high-risk asymptomatic individuals is needed. Even though heart attacks kill and cost more than cancers, as a nation we spend over 20 times more on screening for asymptomatic cancer than for asymptomatic atherosclerotic cardiovascular disease (ASCVD), the underlying cause of heart attacks. Currently, payers only cover screening for risk factors of ASCVD such as blood pressure and blood cholesterol. This approach tends to miss high-risk and over-treat low-risk individuals. Although treadmill stress testing with ECG is not indicated for ASCVD detection in asymptomatic individuals, it is done often, and frequently leads to misleading conclusions or unnecessary downstream diagnostic procedures. For example, former President Clinton had passed his treadmill stress tests for several years during his presidential annual checkup but had a heart attack shortly after his presidency. This common practice is a waste of our limited resources. Instead, a more accurate risk assessment using coronary artery calcium (CAC) testing is available; and has just been adopted by ACC/AHA guidelines, however payers do not cover it. CAC is measured non-invasively with a 5-minute CT-scan of the heart, and costs less than $200, whereas cancer screening with colonoscopy and mammography costs over $3000. There is an opportunity to save lives and dollars if CAC testing is covered for appropriately selected individuals. Texas has already passed HB1290 to mandate CAC coverage. Other states must step up and take actions.