Question

1) Briefly describe how having stiffer central arteries (aorta and carotid arteries) can result in a reduced ability to modulate heart rate by the Vagus nerve (i.e., parasympathetic nervous system).

2) “Hear attacks” primarily result from a sequence of events known as Ischemia-reperfusion. Describe how during ischemia the decrease in intracellular ATP and increase in intracellular hydrogen ions (from anaerobic metabolism) each contribute to an accumulation of sodium inside of myocardial cells.

3) Provide a brief description of how this build-up of sodium ultimately furthers the accumulation of calcium in the cytosol of myocardial cells.

4) During Reperfusion there is both an influx of calcium into the mitochondrial matrix and an increased generation of Reactive oxygen species by the mitochondria. How do these 2 events collectively contribute to mitochondrial rupture and ultimately apoptosis (cell death) of those myocardial cells. Please refer to specific channels, etc. in your response.

5) Exercise training can minimize the amount of damage to the myocardium if an ischemia-reperfusion occurs. Based on evidence (largely from rodent models), how much exercise is needed in order to provide this myocardial protection, and how long does this protection last/persist following cessation of exercise.

6) Exercise training has been shown to increase the expression of ATP-sensitive potassium (KATP) channels on the sarcolemma of myocardial cells. Provide an explanation for how having more sarcolemmal KATP channels can reduce the amount of calcium accumulation in the cytosol during ischemia. Your response should include the function of these channels as well as how they impact action potentials in myocardial contractile cells.

7) Exercise training results in increased intracellular stores of nitrite, including in the myocardium. During myocardial ischemia, nitrite is reduced back to the molecule nitric oxide in those cells. Name 2 proteins or structures that nitric oxide modifies (via nitrosylation), and describe how modification of these proteins prevents mitochondrial damage during reperfusion.

Answer 1

1.

Baroreceptors (carotid artery and aortic arch ) function with changes in pressure responding to change in the tension of arterial wall, in healthy human it has a fast response to changes in blood pressure.

normal mechanism

as blood pressure, increases_stretches baroreceptors_ inhibits sympathetic drive on SinoAtrial node in the heart_Decreased heart rate

when blood pressure decreases_ decrease pressure on baroreceptors_ stimulate sympathetic drive_Inhibits vagal tone_ Heart rate increases

As age increases baroreceptor sensibility decreases and get stiffened, and affect the response to pressure changes. This will affect increased blood pressure variability, inability to respond to sudden changes in blood pressure and the risk of sudden cardiac death.

2.

Tissue injury or death occurs as a result of ischemia insult and then reperfusion.

prolonged ischemia decreases Adenosine Tri-Phosphate( ATP) and cell pH because of anaerobic metabolism and lactate accumulation. Hydrogen ions are more in the cell in this stage, to buffer this condition cell excretes excess hydrogen in exchange of sodium through Na⁺ /H^{+ exchanger.}

3.

ischemia also depletes cellular ATP and increased intracellular pH alters ion exchange, reduces calcium excretion and reduces reuptake of calcium by endoplasmic reticulum leads to accumulation of calcium in the cell. ( decrease in ATP, leads to pass out of potassium from the cell, and movement of sodium and calcium into the cell ).