Robert Kloner

University of Southern California | USC · Department of Medicine

Introduction: Intrinsic frequency (IF) method is a novel systems-based approach that uses a single uncalibrated arterial waveform for the analysis of the left ventricle (LV) and arterial function. In a recent Framingham Heart Study, it was shown that IFs derived from carotid waveforms predict incident of heart failure and composite cardiovascular d...

Background: Nitrates and nitrate-containing compounds are vasodilators used for the treatment of angina and heart failure. Phosphodiesterase type 5 inhibitors used for the treatment of erectile dysfunction are also vasodilators, and when taken together with nitrates, synergistic effects that enhance hypotensive effects may occur. Phosphodiesterase...

Over-the-counter analgesics are used globally for the relief of acute pain. Although effective, these agents can be associated with adverse effects that may limit their use in some people. In the early 2000s, observations from clinical trials of prescription-strength and supratherapeutic doses of nonselective and cyclooxygenase-2-selective nonstero...

Myocardial infarction is a prevalent major cardiovascular event that arises from myocardial ischemia with or without reperfusion, and basic and translational research is needed to better understand its underlying mechanisms and consequences for cardiac structure and function. Ischemia underlies a broad range of clinical scenarios ranging from angin...

A paradox is a seemingly absurd or impossible concept, proposition, or theory that is often difficult to understand or explain, sometimes apparently self-contradictory, and yet ultimately correct or true. How is it possible, for example, that oxygen “a toxic environmental poison” could be also indispensable for life (Beckman and Ames Physiol Rev 78...

Early coronary artery reperfusion improves outcomes for patients with ST-segment elevation myocardial infarction (STEMI), but morbidity and mortality after STEMI remain unacceptably high. The primary deficits seen in these patients include inadequate pump function, owing to rapid infarction of muscle in the first few hours of treatment, and adverse...

Cocaine is the leading cause for drug–abuse-related visits to emergency departments, most of which are due to cardiovascular complaints. Through its diverse pathophysiological mechanisms, cocaine exerts various adverse effects on the cardiovascular system, many times with grave results. Described here are the varied cardiovascular effects of cocain...

Objective: The study is based on previously reported mathematical analysis of arterial waveform that extracts hidden oscillations in the waveform that we called intrinsic frequencies. The goal of this clinical study was to compare the accuracy of left ventricular ejection fraction derived from intrinsic frequencies noninvasively versus left ventri...

Therapeutic hypothermia (TH) is known to protect against ischemia/reperfusion (I/R) injury. One mechanism of I/R injury includes secondary injury due to the inflammatory cascade. We hypothesized that TH reduces the inflammatory response following I/R injury. Rats were randomized to sham, normothermic, or hypothermic groups and subjected to 1 hour o...

Heart failure (HF) is a systemic illness with grave implications for bodily functions. The brain, among other vital organs, often suffers insults as a result of HF, and both anatomic and functional brain abnormalities were found in the HF population. This injury was demonstrated across a wide range of clinical conditions and cardiac functions and w...

The size of the myocardial infarction remains an important therapeutic target, because heart attack size correlates with mortality and heart failure. In this era, myocardial infarct size is reduced primarily by timely reperfusion of the infarct related coronary artery. Whereas numerous pre-clinical studies have shown that certain pharmacologic agen...

At the conclusion of a primary percutaneous coronary intervention for ST-segment elevation myocardial infarction, and after the cardiologist makes certain that there is no residual stenosis following stenting, assessment of coronary flow becomes the top priority. The presence of no-reflow is a serious prognostic sign. No-reflow can result in poor h...

Background: Adjunctive therapies, given in addition to reperfusion to reduce myocardial infarct size, have been disappointing based on clinical trials. New therapeutic targets independent of infarct size modification are needed. The no-reflow phenomenon occurs commonly after the infarct-related coronary artery is opened and predicts poor clinical...

response to a letter to editor on remote ischemic preconditioning by Lalonde et Curnier

PurposeDysfunctional mitochondria are considered to be the major source of intracellular reactive oxygen species and play a central role in the pathophysiology of myocardial ischemia/reperfusion. This study sought to determine effects of mitochondria-targeted cytoprotective peptide SBT-20 on myocardial infarct size in two different models of ischem...

The authors present the first in vivo measurements of L-Glucose and D-Glucose concentrations using millimeter waves. Employing direct injection of solutions into the rat jugular vein, we have been able to correlate immediate changes in blood glucose readings with transmission loss through the ears of anesthetized rats at Ka band (27–40 GHz). The se...

Biomarker measures of infarct size and myocardial salvage index are important surrogate measures of clinical outcomes following a myocardial infarction. However, there is variability in infarct size unaccounted for by conventional adjustment factors. This post-hoc analysis of EMBRACE STEMI trial evaluates the association between left ventricular (L...

numerous studies on this subject. This literature presents some of the most controversial group of papers that I have reviewed, with some studies suggesting that testosterone use is associated with an increase in adverse cardiac events including major adverse cardiac events (cardiovascular death, myocardial infarction, stroke), whereas others sugge...

Ischaemic heart disease (IHD) remains the leading cause of death and disability in Europe and worldwide. A major cause of morbidity and mortality in IHD patients is an acute ST-segment elevation myocardial infarction (STEMI), which despite prompt reperfusion by primary percutaneous coronary intervention (PPCI) has significant mortality (7% death at...

Background: Biomarker measures of infarct size and myocardial salvage index after a myocardial infarction are important surrogate measures of clinical outcomes. However, there is variability in infarct size unaccounted for by conventional adjustment factors. We evaluated the association of the end-diastolic left ventricular (LV) mass and infarct si...

Testosterone (T) is the principal male sex hormone. As men age, T levels typically fall. Symptoms of low T include decreased libido, vasomotor instability, and decreased bone mineral density. Other symptoms may include depression, fatigue, erectile dysfunction, and reduced muscle strength/mass. Epidemiology studies show that low levels of T are ass...

This editorial describes benefits and limitations of remote ischemic conditioning. Remote ischemic conditioning was shown to reduce myocardial intact size in at least 4 sizeable clinical trials of acute myocardial infarction. It was not effective in recent studies of cardiac surgery. Reasons for these differences are discussed.

Angina pectoris is defined as substernal chest pain, pressure, or discomfort that is typically exacerbated by exertion and/or emotional stress, lasts greater than 30 to 60 seconds, and is relieved by rest and nitroglycerin. There are approximately 10 million people in the United States who have angina, and there are over 500 000 cases diagnosed per...

Whether sex affects the acute phase of myocardial ischemia in experimental animal models is currently being debated. Our purpose was to determine if sex influences either the incidence or severity of reperfusion-induced arrhythmias resulting from a brief coronary occlusion. Male and female Sprague-Dawley rats were assigned to the study. Anesthetize...

While progress has been made in improving survival following myocardial infarction, this injury remains a major source of mortality and morbidity despite modern reperfusion therapy. While one approach has been to develop therapies to reduce lethal myocardial cell reperfusion injury, this concept has not translated to the clinics, and several recent...

Aims: Among patients with ST-elevation myocardial infarction (STEMI), reperfusion injury contributes to additional myocardial damage. MTP-131 is a cell-permeable peptide that preserves the integrity of cardiolipin, enhances mitochondrial energetics, and improves myocyte survival during reperfusion. Methods and results: EMBRACE STEMI is a multice...

Aims: We have observed that Bendavia, a mitochondrial-targeting peptide that binds the phospholipid cardiolipin and stabilizes the components of electron transport and ATP generation, improves cardiac function and prevents left ventricular remodeling in a 6week rat myocardial infarction (MI) model. We hypothesized that Bendavia restores mitochondr...

A distinct seasonal pattern in total and cardiovascular death rates has been reported. The factors contributing to this pattern have not been fully explored. Seven locations (average total population 71,354,000) were selected where data were available including relatively warm, cold, and moderate temperatures. Over the period 2004 to 2009, there we...

Background-—The long-term effects of transient hypothermia by the non-invasive ThermoSuit apparatus on myocardial infarct (MI) scar size, left ventricular (LV) remodeling, and LV function were assessed in rat MI model. Methods and Results-—Rats were randomized to normothermic or hypothermic groups (n=14 in each group) and subjected to 30 minutes co...

This study sought to evaluate the safety and efficacy of peripheral vascular interventions performed in a private, outpatient catheterization laboratory. Peripheral vascular interventions have been traditionally performed in the inpatient setting. However, there has been a recent shift away from hospital-based vascular interventions toward outpatie...

Current therapies for myocardial infarction are geared to try to limit ischemic/reperfusion injury by early and complete reperfusion, including percutaneous coronary interventions, antiplatelet agents, and anticoagulants; and attempts to limit post infarction left ventricular remodeling by inhibitors of the renin-angiotensin-aldosterone pathway or...

Purpose: Ischemic preconditioning (IPC) has been used to protect myocardial cells against ischemia-reperfusion injury and is recently utilized for improving exercise performance. It is unknown whether remote IPC (RIPC) to tissues not involved in exercise can induce similar exercise improvements and what " dose " of IPC is necessary to induce exerci...

People often are in the habit of consuming many types of products; some of these products are legal, while others are illegal. Many of these products have profound effects on the cardiovascular system. The chapter will discuss many of these deleterious products, such as tobacco, cocaine, and amphetamines, and will describe their devastating effects...

The Langendorff heart is a modification of the isolated-perfused heart that receives the perfusate solution in a retrograde manner through the aorta. The critical component of the Langendorff heart is the insertion of a cannula, while nutrients and oxygen are supplied via retrograde perfusion. The development of the Langendorff heart has led to con...

The cardiovascular consequences of cocaine use are numerous and can be severe, with mechanisms of cardiotoxicity unique to cocaine that include sympathomimetic effects, blockade of sodium and potassium channels, oxidative stress and mitochondrial damage, and disruption of excitation-contraction coupling. In combination, these effects increase myoca...

IntroductionControversy has arisen over the issue of the cardiovascular safety of testosterone.AimThe aim of this article is to examine the evidence as to the cardiovascular safety involved with the administration of testosterone.MethodsA literature review was performed with regard to cardiovascular safety of testosterone.Main Outcome MeasureThe ma...

In the 1960s and 1970s, the laboratory of Dr. Robert Jennings performed many experimental studies exploring the effect of reperfusion on myocardial pathology using an anesthetized canine model of mechanical proximal circumflex coronary artery occlusion followed by reperfusion [(1–3)][1]. They

A door-to-balloon time of less than 90 minutes is the gold standard for reperfusion therapy to treat acute myocardial infarction (MI). Because 30-day mortality remains ∼10%, new methods must be cultivated to limit myocardial injury. Therapeutic hypothermia has long been experimentally used to attenuate myocardial necrosis during MI with promising r...

: We evaluated the post-myocardial infarction (MI) therapeutic effects of Bendavia. Two hours after coronary artery ligation, rats were randomized to receive chronic Bendavia treatment (n=28) or water (n=26). Six weeks later, Bendavia significantly reduced scar circumference (39.7 ± 2.2 %) compared to water treatment (47.4 ± 0.03 %, p=0.024); and r...

Ranolazine, an inhibitor of the late current of the cardiac action potential (late INa), is a well established clinical treatment for chronic angina. The late INa in cardiac myocytes also plays an important role in the pathophysiology of acute myocardial ischemia and reperfusion, and thus is a potential therapeutic target to ameliorate consequences...

The no-reflow phenomenon occurs when an epicardial coronary artery is reopened following myocardial infarction, but portions of the intramural microvasculature fail to reperfuse. One potential mechanism for this is the presence of fibrin tactoids. In addition, some recent studies have suggested that dabigatran treatment may be associated with incre...

Introduction: Although hypothermia reduces myocardial infarct size, noninvasive and rapid cooling methods are lacking. This study tests the effectiveness of a novel cooling apparatus on myocardial infarct size and no-reflow area in 2 models of coronary artery occlusion (CAO). Methods and results: Animals were randomized to normothermic (N) or hy...

Purpose: Topical capsaicin application was shown to reduce infarct size in experimental animal models. We hypothesized that cardioprotective properties of topical capsaicin application could be related to its hypothermic effect. Methods: In the first arm of the study, anesthetized rats received capsaicin cream (Caps group) or vehicle (Control gr...

Background Our objectives were to characterize functional and structural features of an experimental model of Takotsubo cardiomyopathy, and its response to beta‐blockers. Methods and Results In protocol 1, a dose‐finding study: 69 rats received various doses of isoproterenol (ISO) and echocardiographic and histologic parameters were measured on da...

Although preconditioning remains one of the most powerful maneuvers to reduce myocardial infarct size, it is not feasible in the clinical setting to pretreat patients prior to acute myocardial infarction (MI). The purpose of this study was to investigate the effect of more clinically relevant therapies of remote perconditioning, postconditioning, a...

Marijuana is a very old drug with documented use reaching back to Chinese emperors and Egyptian pharaohs. Ancient civilizations described the medicinal value of marijuana, promoting it for its healing powers, anti-inflammatory properties, and as a treatment for many different disease states.[1][1]

Introduction: A growing number of men are using exogenous testosterone (T) to treat hypogonadism and to enhance athletic performance. However, some studies suggested that T increased adverse cardiovascular events. Although T has been shown to increase apoptosis, its effect on total acute myocardial infarction (MI) size is largely unknown. We hypoth...

Although numerous studies demonstrated that localized delivery of either cells or biomaterials improved postinfarction cardiac function, the underlying mechanisms for this effect remain unclear. We performed a comparison of the effects of fetal, neonatal, and human embryonic stem cell-derived cardiac cell as well as mesenchymal stem cell transplant...

We report the case of a 59-year-old woman who presented with symptoms of angina that was refractory to medical management. Although her cardiac catheterization revealed microvascular coronary artery disease, her symptoms were refractory to optimal medical management that included ranolazine. After undergoing transmyocardial revascularization, her m...

Background: The optimal cell source for cardiac regeneration remains to be determined, and whether chondro-osteogenic mass formation is an adverse effect of stem cell therapy is unclear. In this study, we investigated the fate of human fetal heart-derived stem cells (fHHSC) and human fetal brain-derived stem cells (fHBSC) within the infarcted wall,...

Background: Nitrogen may contribute to reperfusion injury. Some studies have shown that helium as a replacement for nitrogen in breathing gas (heliox) reduces cell necrosis after ischemia/reperfusion when used in a preconditioning fashion (intermittent heliox exposure). Our aim was to test whether heliox, breathed continuously throughout the ischem...

Many studies have shown that when hypothermia is started after coronary artery reperfusion (CAR), it is ineffective at reducing necrosis. However, some suggest that hypothermia may preferentially reduce no-reflow. Our aim was to test the effects of hypothermia on no-reflow when initiated close to reperfusion and 30 minutes after reperfusion, times...

We recently showed that Bendavia, a novel mitochondria-targeting peptide, reduced infarction and no-reflow across several experimental models. The purpose of this study was to determine the therapeutic timing and mechanism of action that underlie Bendavia's cytoprotective property. In rabbits exposed to in vivo ischemia/reperfusion (30/180 min), Be...

Chronic stable angina (CSA) impairs patient quality of life, is associated with increased patient mortality, and is a prominent symptom of coronary artery disease (CAD), the latter being prevalent worldwide in patients. Currently, therapeutic options for patients with CSA include β-blockers, calcium channel blockers, nitrates, and ranolazine. Ranol...

In animal models of coronary artery occlusion and reopening of the -epicardial artery, perfusion defects within the area at risk may develop during reperfusion despite complete reopening of the epicardial artery. These anatomical areas of no-reflow are confined to areas of myocardial necrosis and substantially expand during ongoing reperfusion. Thi...

Recent data from the Massachusetts Male Aging Study (MMAS) have revealed an increasing incidence of hypogonadism within the aging US population. The Massachusetts Male Aging Study estimates indicate that ≈2.4 million men aged 40 to 69 suffer from hypogonadism in the United States.[1][1] The

Marijuana is the most widely used illicit drug, with approximately 200 million users worldwide. Once illegal throughout the United States, cannabis is now legal for medicinal purposes in several states and for recreational use in 3 states. The current wave of decriminalization may lead to more widespread use, and it is important that cardiologists...

The adult mammalian heart has limited capability for self-repair after myocardial infarction. Therefore, therapeutic strategies that improve post-infarct cardiac function are critically needed. The small molecule ICG-001 modulates Wnt signaling and increased the expression of genes beneficial for cardiac regeneration in epicardial cells. Lineage tr...

A previous analysis from Los Angeles showed that death rates increased among hometown fans after losing the Super Bowl in 1980 and decreased after a win in 1984. Data are unavailable in the era of drug-eluting stents, dual antiplatelet therapy, statins, and modern medical therapy. Two high drama and intense Super Bowls were analyzed: NYC beat New E...

Erectile dysfunction (ED) is considered a vascular impairment that shares many risk factors with cardiovascular disease (CVD). A correlation between ED and CVD has been hypothesized, and ED has been proposed as an early marker of symptomatic CVD. To analyze the relationship between ED and CVD, evaluating the pathophysiologic links between these con...

There is continued interest in the concept of limiting myocardial infarct size with adjunctive agents administered along with reperfusion injury; however, there remains considerable controversy in the literature. The purpose of this article is to review the medical literature on clinical trials performed during the past 3 years that have attempted...

Since the discovery of ischemic preconditioning (IPC) 26 years ago, numerous studies attempted to determine the mechanism of this powerful form of cardioprotection. One of the first proposed pathways of IPC suggested that the preconditioning stimulus activated phospholipase C via G-protein, and diacylglycerol released from phospholipid moieties act...

An increasing number of elderly men are receiving exogenous testosterone to treat hypogonadism, low libido, and general weakness.[1][1] The impact of testosterone on the cardiovascular system is controversial. Elderly men are typically at higher risk for adverse cardiovascular events than age-

Ischemia-reperfusion injury occurs during coronary artery bypass graft operations. Strategies are needed to lower the extent of damage. Attempts to find these strategies have been occurring for more than 40 years, with remote ischemic preconditioning being one method. This review provides a look at potential mechanisms involved in remote ischemic p...

Oxygen Supply/Demand Approach to Reducing Infarct Size Great strides have been made in the treatment of acute myocardial infarction (MI). Improved outcomes and reduced mortality are largely the result of opening the occluded infarct artery as soon as possible and by keeping it open. Early reperfusion consistently reduces myocardial infarct size in...

Erectile dysfunction (ED) and cardiovascular disease (CVD) share risk factors and frequently coexist, with endothelial dysfunction believed to be the pathophysiologic link. ED is common, affecting more than 70% of men with known CVD. In addition, clinical studies have demonstrated that ED in men with no known CVD often precedes a CVD event by 2-5 y...

Think of the abstract as a "mini" manuscript with an introduction or background, purpose, methods, results, and conclusion sections. Include the key data only; primary outcome data, some of the secondary data, and safety data, if crucial to the study. In most cases, the abstract should be ≤250 words.

Although significant efforts have been made to improve ST-segment elevation myocardial infarction (STEMI) outcomes by reducing symptom-onset-to-reperfusion times, strategies to decrease the clinical impact of ischemic reperfusion injury have demonstrated limited success. Bendavia, an intravenously administered mitochondrial targeting peptide, has b...

Drugs for erectile dysfunction (ED) may be contraindicated with nitrates commonly used to treat patients with angina pectoris, and certain antianginal therapies may worsen ED. The American Heart Association and the Princeton Consensus Conference panel of experts recommend that patients with coronary artery disease and ED who experience angina pecto...

The effects of phosphodiesterase type 5 inhibitors on vasodilation mediated via nitric oxide-cyclic guanosine monophosphate are well described. Less is known about other mechanisms through which phosphodiesterase type 5 inhibitors benefit endothelial function, including normalization of serum biomarkers, increased levels of endothelial progenitor c...

Aims: We determined whether implantation of heart tissue-derived decellularized matrix, which contains native biochemical and structural matrix composition, could thicken the infarcted left ventricular (LV) wall and improve LV function in a rat myocardial infarction model. Methods and results: Myocardial infarction was induced by left coronary l...