Uptake of household disinfection kits as an additional measure in response to a cholera outbreak in urban areas of Haiti.

Médecins Sans Frontières-Operational Centre Amsterdam piloted the distribution of household disinfection kits (HDKs) and health promotion sessions for cholera prevention in households of patients admitted to their cholera treatment centres in Carrefour, Port au Prince, Haiti, between December 2010 and February 2011. We conducted a follow-up survey with 208 recipient households to determine the uptake and use of the kits and understanding of the health promotion messages. In 61% of surveyed households, a caregiver had been the recipient of the HDK and 57.7% of households had received the HDKs after the discharge of the patient. Among surveyed households, 97.6% stated they had used the contents of the HDK after receiving it, with 75% of these reporting using five or more items, with the two most popular items being chlorine and soap. A significant (p < 0.05) increase in self-reported use items in the HDK was observed in households that received kits after 24 January 2011 when the education messages were strengthened. To our knowledge, this is the first time it has been demonstrated that during a large-scale cholera outbreak, the distribution of simple kits, with readily available cleaning products and materials, combined with health promotion is easy, feasible, and valued by the target population.

Increased susceptibility to ventricular arrhythmias in hypertensive paraplegic rats.

Individuals with spinal cord injury (SCI) between thoracic vertebrae four (T4) and five (T5) have elevated levels of sympathetic activity to the heart. Notably, female spontaneously hypertensive rats (SHR) also have increased cardiac sympathetic nerve activity (SNA). Since elevated levels of cardiac SNA increase the risk for cardiac arrhythmias, we tested the hypothesis that hypertensive, paraplegic rats have an increased susceptibility to ventricular arrhythmias. To test this hypothesis, intact (n = 7) and paraplegic hypertensive rats (n = 6) were chronically instrumented with silver stimulating electrodes on the left ventricle, electrocardiogram (ECG) recording electrodes and an arterial catheter. After recovery, the effective refractory period, the electrical stimulation threshold to induce ventricular arrhythmias and cardiac sympathetic tonus (ST) were determined. Paraplegic rats had a lower effective refractory period (35%), lower electrical stimulation threshold to induce ventricular arrhythmias (62%), and higher cardiac ST (84%). These data document an increased susceptibility to ventricular arrhythmias in hypertensive, paraplegic rats.

Daily exercise reduces measures of heart rate and blood pressure variability in hypertensive rats.

This study was designed to test the hypothesis that daily spontaneous running (DSR) reduces measures of heart rate and blood pressure variability in spontaneously hypertensive rats (SHR). After 8 weeks of DSR or sedentary control, rats were chronically instrumented with arterial catheters. Daily exercise reduced most measures of heart rate (HR) and blood pressure variability. Specifically DSR decreased heart rate, Low Frequency Power (LF: 0.19-0.61 Hz), and Low Frequency/High Frequency (HF: 1.2-2.5 Hz) ratio of HR. Furthermore, Total Power (TP), LF power, and LF/HF ratio of systolic blood pressure were reduced by daily spontaneous running. Finally, TP, LF and HF powers and LF/HF ratios of diastolic blood pressure were reduced by daily spontaneous running. These data demonstrate that daily exercise reduces sympathetic activity and possibly increases cardiac reserve in hypertensive animals.

Sino-aortic denervation alters the hemodynamic response to exercise in hypertensive rats.

The effect of sino-aortic denervation (SAD) on the heart rate (HR), arterial pressure (AP) and regional blood flow responses during dynamic exercise was examined in spontaneously hypertensive rats (SHR). Intact (n= 14) and SAD (n= 17) rats were instrumented with arterial catheters and mesenteric and iliac Doppler ultrasonic flow probes. After recovery, all rats underwent a graded exercise test. Heart rate increased significantly during exercise in intact and SAD rats. There was no significant difference in the steady state heart rate response to exercise in the intact and SAD rats. Arterial pressure increased during exercise in the intact rats. In sharp contrast, arterial pressure decreased during exercise in the SAD rats. Iliac vascular conductance increased during exercise in the intact and SAD rats. The increase in iliac vascular conductance during exercise was significantly greater in the SAD rats. Mesenteric vascular conductance decreased during exercise in the intact and SAD rats. The decrease in mesenteric vascular conductance during exercise was significantly attenuated in the SAD rats. Results suggest that functioning arterial baroreceptors are required for the typical hemodynamic responses during dynamic treadmill running in hypertensive rats.

Mechanisms mediating NTS P2x receptor-evoked hypotension: cardiac output vs. total peripheral resistance.

We have previously shown that P2x purinoceptor activation in the subpostremal nucleus tractus solitarius (NTS) produces dose-dependent decreases in mean arterial pressure (MAP), heart rate, efferent sympathetic nerve activity, and significant peripheral vasodilation. However, the relative roles of cardiac output (CO) and total peripheral resistance (TPR) in mediating this depressor response are unknown. Bradycardia does not necessarily result in decreased CO, because, with the greater filling time, stroke volume may increase such that CO may be unchanged. We measured changes in CO (via a chronically implanted flow probe on the ascending aorta) and MAP in alpha-chloralose- and urethane-anesthetized male Sprague-Dawley rats in response to microinjection of the selective P2x purinoceptor agonist alpha,beta-methylene ATP (25 and 100 pmol/50 nl) into the subpostremal NTS. TPR was calculated as MAP/CO. At the low dose of NTS P2x purinoceptor agonist, the reduction in MAP was primarily mediated by reductions in TPR (-31.3 +/- 3.3%), not CO (-8.7 +/- 1.7%). At the high dose, both CO (-34.4 +/- 6.6%) and TPR (-40.2 +/- 2.5%) contribute to the reduction in MAP. We conclude that the relative contribution of CO and TPR to the reduction in MAP evoked by NTS P2x purinoceptor activation is dependent on the extent of P2x purinoceptor activation.

Central baroreflex resetting as a means of increasing and decreasing sympathetic outflow and arterial pressure.

The arterial baroreflex has two important functions. First, the arterial baroreflex is a negative feedback reflex that regulates arterial pressure around a preset value called a set or operating point. Second, the arterial baroreflex also establishes the prevailing systemic arterial pressure when the operating point is reset. That is, modulating the response of barosensitive neurons in the central nervous system (CNS) establishes the operating point or prevailing systemic arterial pressure. Therefore, the operating point of the arterial baroreflex is not fixed, but is variable over a wide range of pressures and is determined by a variety of inputs from the peripheral and central nervous systems. At the onset of dynamic exercise, heart rate (HR) and sympathetic nerve activity (SNA) increase abruptly and dramatically. The initial increase in HR and SNA is mediated by central command. Central command operates by resetting the operating point of the arterial baroreflex to a higher pressure. In this situation, the operating point of the arterial baroreflex is above the prevailing arterial pressure, which elicits a blood pressure error. This error is corrected by activating SNA and inhibiting parasympathetic nerve activity, which increases cardiac output and peripheral resistance and, consequently, arterial pressure. After exercise, loss of central command and enhanced activity of the cardiopulmonary reflex resets the operating point of the arterial baroreflex to a lower pressure. In this situation, the operating point of the arterial baroreflex is below the prevailing arterial pressure, which elicits a blood pressure error. This error is corrected by inhibiting SNA, which decreases peripheral resistance and consequently arterial pressure. In these situations, central resetting of the arterial baroreflex is a means of increasing and decreasing sympathetic outflow and arterial pressure.

Central blockade of vasopressin V(1) receptors attenuates postexercise hypotension.

We tested the hypothesis that central arginine vasopressin (AVP) mediates postexercise reductions in arterial pressure (AP) and heart rate (HR). To test this hypothesis, nine spontaneously hypertensive rats (SHR) were instrumented with a 22-gauge stainless steel guide cannula in the right lateral cerebral ventricle and with a carotid arterial catheter. After the rats recovered, AP and HR were assessed before and after a single bout of dynamic exercise with the central administration of vehicle or the selective AVP V(1)-receptor antagonist d(CH(3))(5) Tyr(Me)-AVP (AVP-X). AP and HR were significantly decreased below preexercise values with central administration of vehicle [P < 0.05, change (Delta)-21 +/- 4 mmHg and Delta-20 +/- 6 beats/min, respectively]. In sharp contrast, after exercise with central administration of AVP-X, both AP (Delta+8 +/- 5 mmHg) and HR (Delta+24 +/- 9 beats/min) were not significantly different from preexercise values (P > 0.05). Furthermore, AVP-X at rest did not significantly alter AP (181 +/- 11 vs. 178 +/- 11 mmHg, P > 0.05) or HR (328 +/- 24 vs. 331 +/- 22 beats/min, P > 0.05). Thus central blockade of AVP V(1) receptors prevented postexercise reductions in AP and HR. These data suggest that AVP, acting within the central nervous system, mediates postexercise reductions in AP and HR in the SHR.

Recovery from carotid artery catheterization performed under various anesthetics in male, Sprague-Dawley rats.

This study was designed to determine the time to recovery from carotid artery catheterization using multiple criteria and to compare recovery times between three common anesthetics. Male Sprague-Dawley rats, chronically instrumented with radio-telemetry transmitters, were anesthetized with sodium pentobarbital, halothane or a mixture of ketamine, xylazine and acepromazine before an indwelling catheter was placed in the carotid artery. The procedure was completed in less than 15 min. Changes in body weight, food and water consumption, blood pressure, heart rate and activity were used to determine recovery. As judged by recovery of body weight, animals anesthetized with each of the anesthetics recovered by the 4th day after catheterization. Food and water consumption normalized by 1-2 days after surgery. Heart rates and blood pressures during the light phase of the photoperiod were significantly increased for 2 days by all anesthetics. During the dark phase of the photoperiod, heart rates and blood pressures were not significantly affected by pentobarbital or halothane anesthesia, but were significantly decreased and increased respectively on the night immediately following surgery in the ketamine / xylazine / acepromazine-anesthetized rats. Delayed elevations of heart rate were observed in pentobarbital and halothane anesthetized rats on days and/or nights 5 and 6 post surgery. Animal activity patterns during the light phase of the photoperiod were not affected by pentobarbital or halothane, but were increased by ketamine 2 days after surgery. During the dark phase, halothane transiently reduced activity whereas ketamine-anesthetized rats showed reduced activity for 4 nights post surgery. These studies show that recovery depends on the criteria selected and the anesthetic used, but, in general, 2-4 days were required for recovery from this relatively simple procedure.

In vivo regulation of Na/Ca exchanger expression by adrenergic effectors.

The Na/Ca exchanger encoded by the NCX1 gene plays an important role in calcium homeostasis in cardiac muscle. We previously identified three in vitro signaling pathways that are of major importance in the regulation of Na/Ca exchanger gene expression in neonatal cardiac myocytes, the protein kinase A (PKA) and protein kinase C (PKC) pathways, and intracellular Ca(2+). To determine whether these pathways are important in vivo, we stimulated the PKA and PKC pathways and examined functional expression of the Na/Ca exchanger in adult rat heart. After a 3- and 7-day treatment, norepinephrine (200 microg x kg(-1) x h(-1)), isoproterenol (150 microg x kg(-1) x h(-1)), and phenylephrine (200 microg x kg(-1) x h(-1)) each stimulated a significant increase in NCX1 mRNA levels (35-85%, P < 0.05). Norepinephrine also stimulated a 35% increase in protein abundance (P < 0.05), a 20% decrease in relaxation duration (P < 0.05), and a 25% reduction in the fluorescence decay constant (P < 0.05) after a 7-day treatment. We conclude that a 7-day treatment of alpha- and beta-adrenergic agonists increases the expression of functional Na/Ca exchangers in adult rat heart.

Active learning of respiratory physiology improves performance on respiratory physiology examinations.

Active involvement in the learning process has been suggested to enhance creative thinking, judgement, interpretation, and problem-solving skills. Therefore, educators are encouraged to create an active-learning environment by incorporating active-learning strategies into the class. However, there is very little documentation of the effectiveness of active-learning strategies. Furthermore, faculty are often reluctant to incorporate new strategies without documentation of the effectiveness of these strategies. To address this concern, we compared the performance of two individual classes on an identical respiratory physiology examination. One class was taught respiratory physiology using active-learning strategies. The other class was taught respiratory physiology using the traditional lecture format. The results document that students who learned using active-learning strategies did significantly better (P < 0.05) on the respiratory physiology examination than students who learned by the traditional lecture format (61 +/- 2.2 vs. 86 +/- 1.0). Thus, by actively involving students in the learning process, academic performance is enhanced.

Inactivation of one copy of the mouse neurotrophin-3 gene induces cardiac sympathetic deficits.

Whether two copies of the neurotrophin-3 (NT3) gene are necessary for proper development of cardiac sympathetic innervation was investigated in mice carrying a targeted inactivation of the NT3 gene. Heterozygous (+/-) and null (-/-) mutant mice had fewer stellate ganglion neurons than did wild-type (+/+) mice at postnatal day 0 (P0 or birth), and this deficit was maintained between adult (P60) +/- and +/+ mice. The sympathetic innervation of the heart matured postnatally in +/+ and +/- mice. Tyrosine hydroxylase (TH)-positive axons were restricted largely to the epicardium at P0, were concentrated around large blood vessels in the myocardium at P21, and were present among cardiac myocytes at P60. Cardiac norepinephrine (NE) concentrations paralleled the growth of the sympathetic axons into the heart. NE concentrations were equivalent among +/+, +/-, and -/- mice at birth, but differences between +/- and +/+ mice increased with age. Adult +/- mice also exhibited lower resting heart rates and sympathetic tonus than +/+ mice. Thus deletion of one copy of the NT3 gene translates into anatomical, biochemical, and functional deficits in cardiac sympathetic innervation of postnatal mice, thereby indicating a gene-dosage effect for the NT3 gene.

Daily exercise attenuated the sympathetic component of the spontaneous arterial baroreflex control of heart rate in hypertensive rats.

The influence of daily spontaneous running on the sympathetic and parasympathetic components of the spontaneous arterial baroreflex control of heart rate was examined in 22 female spontaneously hypertensive rats [12 sedentary and 10 daily spontaneous running]. Following 8 weeks of sedentary control or daily spontaneous running, animals were chronically instrumented with an arterial catheter. Daily spontaneous running resulted in an increased heart weight/body weight ratio (5.2 +/- 0.27 vs 4.3 +/- 0.01 g/kg) and a resting bradycardia (321+/- 8 bpm vs 360 +/- 6). The spontaneous changes in arterial pressure and the reflex responses of heart rate were examined under three experimental conditions: 1) pre-blockade, 2) following beta1-adrenergic receptor blockade, and 3) following muscarinic-cholinergic receptor blockade. Daily spontaneous running attenuated the spontaneous gain of the arterial baroreflex control of heart rate (56%). After muscarinic-cholinergic receptor blockade, the spontaneous gain remained reduced in daily spontaneous running rats (57%). In contrast, after beta1-adrenergic receptor blockade the spontaneous gain was not different between sedentary control and daily spontaneous running animals. Results demonstrate that daily spontaneous running decreased the sympathetic component resulting in an apparently greater influence of the parasympathetic component on the spontaneous arterial baroreflex control of heart rate.

Autonomic and endothelial dysfunction in experimental diabetes.

The effect of streptozotocin induced diabetes on autonomic regulation of heart rate and endothelial function was examined in Sprague-Dawley rats. Weanling rats (3-4 weeks of age) of either sex were randomly assigned to a non-diabetic (male 5, female 6) or diabetic (male 4, female 5). Diabetes was induced with a single intraperitoneal (IP) injection of streptozotocin (STZ, 100 mg/kg). Nondiabetic rats received an IP injection of saline. Eight weeks after injection, rats were chronically instrumented with a left jugular venous catheter and a left carotid arterial catheter. After recovery (5 days) cardiac sympathetic tonus, parasympathetic tonus and intrinsic heart rate were determined. On an alternative day, the pressor response to nitric oxide synthase inhibition (NOS-X) was determined in areflexic rats. Cardiac sympathetic tonus (72 +/- 13 vs. 41 +/- 7), parasympathetic tonus (-51 +/- 10 vs. -22 +/- 7), and intrinsic heart rate (368 +/- 6 vs. 292 +/- 9), were reduced in diabetic rats. Furthermore, diabetic rats had a smaller pressor response (A33 +/- 7 vs. A66 +/- 5) to NOS-X. These results document impaired autonomic control of heart rate and endothelial dysfunction in 8-week streptozotocin induced diabetic rats.

"Virtual" experiment for understanding the electrocardiogram and the mean electrical axis.

Educators have placed an emphasis on the development of laboratory materials that supplement the traditional lecture format. The laboratory materials should encourage active learning, small group discussion, and problem-solving skills. To this end, we developed a virtual experiment designed to introduce students to the theory and application of the electrocardiogram (ECG) and the mean electrical axis (MEA). After reviewing background material, the students will analyze ECG recordings from two individuals who underwent a series of experimental procedures. The students are challenged to reduce and analyze the data, calculate and plot the MEA, and answer questions related to the theory and application of the ECG. In conducting the virtual experiment, students are introduced to inquiry-based learning through experimentation.

Post-exercise elevations in sympathetic nerve activity and baroreflex function in normotensive rabbits.

We tested the hypothesis that a single bout of dynamic exercise reduces post-exercise arterial pressure, heart rate, and renal sympathetic nerve activity and attenuates the arterial baroreflex control of heart rate and renal sympathetic nerve activity in normotensive New Zealand White rabbits. Animals were chronically instrumented with right jugular venous and left femoral arterial catheters, and electrodes around the renal sympathetic nerve. Arterial pressure, heart rate, and renal sympathetic nerve activity were recorded for two hours pre-exercise and two hours after a single bout of treadmill exercise (post-exercise). Post-exercise heart rate, arterial pressure, and renal sympathetic nerve activity were elevated above pre-exercise values (71+/-3 bpm, 13+/-1 mmHg, and 80+/-21%, respectively). These data demonstrate that normotensive rabbits do not exhibit post-exercise hypotension, due in part to elevations in sympathetic nerve activity. In addition, arterial baroreflex regulation of heart rate and renal sympathetic nerve activity were determined pre- and post-exercise. Exercise shifted the baroreflex function curve for heart rate and renal sympathetic nerve activity upward and to the right without a change in gain. These data suggest that post-exercise elevations in sympathetic nerve activity are due, in part, to an elevation of the operating point of the arterial baroreflex to a higher pressure. These responses in normotensive rabbits contrast sharply with the responses in hypertensive individuals and animals. Understanding the mechanisms contributing to the differences between hypertensive and normotensive subjects may lead to measures designed to lower arterial pressure in hypertensive individuals.

Arterial baroreflex regulation of regional vascular conductance at rest and during exercise.

We tested the hypothesis that dynamic exercise resets the operating point and attenuates the spontaneous gain of the arterial baroreflex regulation of mesenteric and hindlimb vascular conductance in hypertensive rats. Eleven adult male spontaneously hypertensive rats were chronically instrumented with left carotid arterial catheters and Doppler ultrasonic flow probes around the superior mesenteric and left common iliac arteries. After the rats recovered, arterial baroreflex function was examined by recording reflex changes in conductance in response to spontaneous changes in mean arterial pressure before exercise and during steady-state treadmill running at 6 and 18 m/min. Dynamic exercise reduced the spontaneous baroreflex gain of mesenteric conductance (by 51 and 36%) and maximum mesenteric conductance (by 24 and 32%) at 6 and 18 m/min, respectively. In sharp contrast, dynamic exercise increased the spontaneous maximum iliac conductance (by 32 and 47%) without changing the spontaneous gain. Sinoaortic denervation eliminated the relationship between mean arterial pressure and conductance by reducing the mesenteric (92%) and iliac (68%) vascular conductance gain. These results demonstrate that dynamic exercise has differential effects on the regulation of mesenteric and iliac vascular conductance in hypertensive rats.

Daily exercise attenuates the development of arterial blood pressure related cardiovascular risk factors in hypertensive rats.

This study was designed to test the hypothesis that daily spontaneous running (DSR) attenuates the development of blood pressure-related cardiovascular disease risk factors (BP-related CVD risk factors) in spontaneously hypertensive rats (SHR). After 8 weeks of DSR or sedentary control, rats were chronically instrumented with arterial catheters. Daily exercise attenuated the development of all measures of BP-related CVD risk factors. Specifically DSR attenuated the increase in systolic blood pressure (delta--22 mmHg), systolic blood pressure variability (delta--2.5 mmHg), and systolic blood pressure load (delta--27%). Similarly, DSR attenuated the increase in diastolic blood pressure (delta--15 mmHg), diastolic blood pressure variability (delta--1.19 mmHg), and diastolic blood pressure load (delta--17%). Finally, DSR attenuated the development of tachycardia (delta--63 bpm). These data demonstrate that daily exercise attenuates the development of hypertension and tachycardia in animals predisposed to hypertension.

Who wants to be a physician? An educational tool for reviewing pulmonary physiology.

Traditional review sessions are typically focused on instructor-based learning. However, experts in the field of higher education have long recommended teaching modalities that incorporate student-based active-learning strategies. Given this, we developed an educational game in pulmonary physiology for first-year medical students based loosely on the popular television game show Who Wants To Be A Millionaire. The purpose of our game, Who Wants To Be A Physician, was to provide students with an educational tool by which to review material previously presented in class. Our goal in designing this game was to encourage students to be active participants in their own learning process. The Who Wants To Be A Physician game was constructed in the form of a manual consisting of a bank of questions in various areas of pulmonary physiology: basic concepts, pulmonary mechanics, ventilation, pulmonary blood flow, pulmonary gas exchange, gas transport, and control of ventilation. Detailed answers are included in the manual to assist the instructor or player in comprehension of the material. In addition, an evaluation instrument was used to assess the effectiveness of this instructional tool in an academic setting. Specifically, the evaluation instrument addressed five major components, including goals and objectives, participation, content, components and organization, and summary and recommendations. Students responded positively to our game and the concept of active learning. Moreover, we are confident that this educational tool has enhanced the students' learning process and their ability to understand and retain information.

Peer instruction improves performance on quizzes.

Peer instruction is a cooperative-learning technique that promotes critical thinking, problem solving, and decision-making skills. Benson's think-pair-share and Mazur's peer-instruction techniques are simple cooperative exercises that promote student's participation in class and increase student's interaction with each other and with the instructor in a large classroom. We borrowed concepts from Benson and Mazur and applied these concepts to enhance student involvement during the respiratory component of the medical physiology class. The medical physiology class consisted of 256 first-year medical students. The peer-instruction technique was used for 10 classes. Each class of 50 min was divided into three or four short presentations of 12-20 min. Each presentation was followed by a one-question, multiple-choice quiz on the subject discussed. Questions ranged from simple recall to those testing complex intellectual activities. Students were given 1 min to think and to record their first answer. Subsequently, students were allowed 1 min to discuss their answers with their classmates and possibly correct their first response. The percentage of correct answers increased significantly (P < 0.05) after discussion for both recall and intellectual questions. These data demonstrate that pausing three to four times during a 50-min class to allow discussion of concepts enhanced the students level of understanding and ability to synthesize and integrate material.

Daily exercise enhances acetylcholine-induced dilation in mesenteric and hindlimb vasculature of hypertensive rats.

The effect of daily spontaneous running (DSR) on endothelial function was examined in spontaneously hypertensive rats (SHR). Following 8-11 weeks of DSR (n=15) or sedentary control (SED, n=15), rats were instrumented with arterial and venous catheters and mesenteric and iliac Doppler ultrasonic flow probes. Hemodynamic responses to vasodilator-mediated substances were determined under two experimental conditions; 1) bolus injection of indomethacin (10 mg/kg) and 4 bolus doses of acetylcholine (0.5-2.0 microg/kg); 2) bolus injection of N(omega)-nitro-L-arginine (5 mg/kg) and 4 bolus doses of nitroglycerin (3-12 microg/kg). Hindlimb vascular conductance decreased more in response to indomethacin in DSR vs. SED rats (-18.3+/-2.8% vs. -10.4+/-2.5%). However, the mesenteric or hindlimb vascular conductance responses to N(omega)-nitro-L-arginine were not different between DSR and SED rats. DSR also enhanced mesenteric and hindlimb vascular conductance responses to acetylcholine. Results suggest that DSR enhances acetylcholine-induced vasodilation in SHR.