Remote ischemic preconditioning (RIPC) occurs when blood flow to an arm a leg is restricted to protect other organs from a subsequent event of lack of blood flow. RIPC is similar to the cardioprotective effect that occurs with exercise that activates the body's protective functions.
Pressure on the arm and forearm restricts blood flow:
This triggers a pain signal to the brain (neuro signal) that prepares the body for a cardiac event. This happens partially due to decreasing the amount of energy that the tissue needs to survive by increasing the parasympathetic tone (rest and relaxation). There is also improved flow of blood by causing dilation of the arteries. It also diminishes the inflammatory response and prepares the immune system by reducing the attacking orders that the body produces (chemokines). Dr. Rubinstein aims to use RIPC to precondition the heart, acting as a stimulus before ischemia occurs.
Our heart constantly needs blood in order to function and supply nutrients for the rest of our body. The arteries that give blood to the heart are called the coronary arteries. When the arteries narrow or become completely blocked, the blood flow is disrupted, resulting in a heart attack. The narrowing happens when a plaque, which is made of cholesterol, white blood cells, and other fatty deposits, build up in the coronary arteries. The damage happens in two stages:
Ischemic injury occurs when the blood flow to the heart is blocked by an occlusion of one of the arteries that perfuses the heart (known as coronary arteries). During the time that there is no blood flow the heart cells begin starving for nutrients and oxygen. The cells try to salvage themselves by stretching their nutrient supply, but unless flow is returned the heart tissue will die from lack of flow.
Once the blood supply to heart is restored, the extent of injury increases do to reperfusion injury, When oxygen is restored, free radicals, such as superoxide and hydrogen peroxide, are formed. All of these free radicals cause oxidative cell damage, and this cell damage leads to the synthesis of inflammatory cytokines. These cytokines are what injure areas other than the heart, such as the lungs.
1 in every 4 deaths in the US can be attributed to heart disease.Heart disease is the leading cause of death for both men and women.Every year about 735,000 Americans have a heart attack.
Reference:heart.org
Heart disease is the leading cause of death in the US and includes conditions that affect the structures or function of the heart.
Reference:cdc.gov
There are different types of heart disease with the most well-known being heart attacks. Almost one million Americans suffer a heart attack, or myocardial infarction, each year.
Reference:heart.org
Tefillin are black leather boxes with leather straps traditionally used by Orthodox Jewish men. They are usually worn on the non-dominant arm during prayer and wrapped tightly around the arm. Tefillin is worn for about 30 minutes each day, except holidays and the Sabbath.
Reference: journals.physiology.orglink.springer.com
Tefillin is part of the Jewish tradition and involves wrapping tightly, but not to the point of occlusion, the non-dominant arm, forearm, and hand in a leather strap for prayer and meditation. Limitation of blood flow to an arm or leg has been previously found to have potential health benefits. Due to the tightly wrapped strap around the arm, which constricts blood flow, tefillin induces a RIPC-like effect. Dr. Rubinstein recently conducted a study, which strongly suggested that the practice of tefillin may reduce the damage to the heart following a heart attack.
The nervous system is stimulated and increases parasympathetic tone. When RIPC is induced through astimulus in the limb, an electrical signal travels to the brain, which in turn stimulates the vagus nerve. The vagus nerve is a key part of the parasympathetic system, which sends signals to lower the heart rate. Thisresults in a lower need for energy and therefore a degree of cardio protection.
Improves blood Flow. When RIPC is stimulated through a limb, it produces signaling molecules called chemokines that cause the arteries to dilate and therefore perfuse more blood to a tissue that is damaged, such as during a heart attack.
Diminishes inflammatory response. There is also lower release of other chemokines that result in a decreased inflammatory response resulting in less tissue damage and therefore cardio protection.
Studies have shown that Orthodox Jews are at lower risk of dying from heart disease than their non-Orthodox counterparts. One difference between the two groups is that the Orthodox Jews wear tefillin on an almost daily basis for about 30 minutes. The forearm has a partial occlusion of blood flow since the method via which it is worn does induce what some describe as a tight or uncomfortable feeling in the forearm and hand. The Rubinstein lab was inspired by this technique and saw this as a potential method to induce RIPC. The lab has since been studying tefillin’s potential for producing a cardioprotective effect.
The references for this are:
• Goldbourt U, Yaari S, Medalie JH. Factors predictive of long-term coronary heart disease mortality among 10,059 male Israeli civil servants and municipal employees. A 23-year mortality follow-up in the Israeli Ischemic Heart Disease Study. Cardiology 82: 100–121, 1993. doi:10.1159/000175862.
• Kark JD, Shemi G, Friedlander Y, Martin O, Manor O, Blondheim SH. Does religious observance promote health? mortality in secular vs religious kibbutzim in Israel. Am J Public Health 86: 341–346, 1996. doi:10.2105/AJPH.86.3.341.
Nerve cells transmit electrical
signals to brain
Brain stimulates vagus nerve
Vagus nerve sends signals to heart
Nerve cells transmit electrical
signals to brain
Chemokines create anti-inflammatory response
Background: RIPC, created by short bursts of ischemia/reperfusion, has not been successfully taken to the bedside. Several large population studies have found that self-identified Orthodox Jewish males (which wear tefillin almost daily) have decreased cardiovascular mortality compared to non-Orthodox counterparts.
Hypothesis: Wearing tefillin induces an RIPC-like effect, thus positively impacting the heart and preconditioning it for a cardiac event. Hypothesis: Wearing tefillin induces an RIPC-like effect, thus positively impacting the heart and preconditioning it for a cardiac event.
Objectives: To assess whether tefillin use elicits a remote ischemic preconditioning (RIPC) effect in subjects with both acute and chronic use.
Participants: Twenty Jewish men were enrolled, 9 daily tefillin users (conditioned) and 11 non-users of tefillin as controls (naïve).
Methods: Subjects were evaluated for adherence to traditional Jewish practice, had vital signs measured, blood drawn for analysis of circulating cytokines and monocyte functional assays and underwent brachial flow mediated dilation to evaluate vascular reactivity at baseline (basal) and after 30 minutes of using tefillin (acute treatment).
Results: Chronic use of tefillin in Orthodox Jewish males was associated with increased blood flow/velocity and decreased markers of inflammation including monocyte chemotaxis and adhesion versus Jewish males that do not usually wear tefillin. Acute use of tefillin in both subject populations augmented brachial artery diameter and blood flow, while not affecting inflammatory or monocyte profiles compared to baseline.
Conclusions: Acute tefillin use improves vascular function while chronic tefillin use is associated with an anti-inflammatory RIPC-like phenotype. Our data suggests that tefillin results in a RIPC-like phenotype with subjects exhibiting improved blood flow and reactivity parameters and decreased inflammation and monocyte reactivity.
Reference: journals.physiology.org
Local ischemic preconditioning. Dr. Charles E Murry and colleagues conducted a study on dogs and found that temporary cross-clamping of the main heart artery in dogs protected the same territory of the heart against an ischemic event.
References: ahajournals.org
Remote preconditioning. The term “remote” was used when scientists observed that the cross-clamping on the right side of the heart protected the left side from ischemia.
References: pubmed.ncbi.nlm.nih.gov
Limb induced remote preconditioning was established when temporary cross-clamping of the leg of a rabbit protected the heart from an ischemic event.
References: ahajournals.org
Doctors from the Hospital for Sick Children in Toronto demonstrated that fully occluding the blood flow to the arm via a non-invasive method produced a similar effect to that observed in the animal studies.
References: pubmed.ncbi.nlm.nih.gov
Dr. Rubinstein studies the effects of tefillin for heart preconditioning, finds that tefillin induces remote ischemic preconditioning pathways in healthy men.
References: journals.physiology.org
Jack Rubinstein, MD, was born and raised in Mexico City, where he completed medical training. Thereafter he pursued internal medicine and cardiology training in the US and is now an Associate Professor in the Division of Cardiovascular Health and Disease at the University of Cincinnati. He has an active inpatient and outpatient clinical practice in general cardiology with a focus on echocardiography.
Dr. Rubinstein heads his translational science laboratory that has been funded at various stages from by the NIH, VA and AHA as well as a number of internal and external funding mechanisms. He also directs the Physician Scientist Training Program for the Department of Internal Medicine and is the medical director of the Clinical Research Unit at the Cincinnati VAMC.
Dr. Rubinstein’s work in the field has been presented by international media and has been translated into over ten languages.
Translational Medicine: His research focuses on finding the shortest path possible in order to bring basic science discoveries to the bedside, including novel observations regarding ischemic preconditioning and drug repurposing for the treatment of heart failure.
RIPC: His laboratory work in ischemic preconditioning was inspired by the Jewish tradition of wearing phylacteries (or tefillin) that are placed by tightly wrapping the non-dominant arm with a leather band.
A critical, uncensored look into the American health care system
The Perfect Dose makes us think critically about the way America views medicine. The story follows a physician-scientist who has discovered a life-saving medication, though the path to get the medication to patients is complicated by our profit-driven healthcare system. The story lets the reader consider the true price of medicine: who should pay for them, how much should they cost, and who should pay for the development of drugs that can potentially save millions of lives. The novel, published in 2018, explores several aspects of not only the healthcare system but also the labs, clinics, and hospitals where life and death decisions are made.
Dr. Rubinstein’s writing journey began during the 2016 elections when he found himself desperate to explain the complex healthcare issues to the public in a way that cuts through partisan talking points with a sometimes raunchy, frequently entertaining narrative.
