The mechanical and electrical behavior of the heart can be critically and permanently impaired by prolonged reductions in coronary blood flow, also known as myocardial ischemia. One of the most common causes of serious cardiac disease is diminished coronary blood flow resulting from coronary artery disease, usually coronary atherosclerosis. This can lead to global ischemia, affecting the entire ventricle, or regional ischemia, affecting only a fraction of the ventricle. The impairment in mechanical contraction of the affected myocardium is not only due to the reduced delivery of oxygen and metabolic substrates, but also the accumulation of potentially harmful substances such as potassium, lactic acid, and hydrogen ions in the cardiac tissues. If the reduction in coronary flow to any region of the heart is severe and prolonged enough, it can result in necrosis of the affected cardiac cells.

Myocardial hibernation refers to the phenomenon where cellular metabolism is downregulated in cells whose function is impaired due to inadequate delivery of oxygen and nutrients. This condition mainly occurs in patients with coronary artery disease who have persistently and significantly diminished coronary blood flow and impaired mechanical function of the heart. However, if coronary blood flow is restored to normal through bypass surgery or angioplasty, the mechanical function of the heart returns to normal as well.

The skin has relatively small O2 and nutrient requirements compared to other body tissues. Cutaneous blood flow is not primarily regulated by the supply of oxygen and nutrients, but rather by the need to maintain a constant body temperature. As a result, the skin undergoes wide fluctuations in blood flow depending on whether the body needs to lose or conserve heat. Mechanisms responsible for alterations in skin blood flow are activated in response to changes in ambient and internal body temperature.

Various surgical attempts have been made to enhance the development of coronary collateral vessels, but the techniques used do not increase collateral circulation beyond that produced by coronary artery narrowing alone. When discrete occlusions or severe narrowing occurs in coronary arteries, such as in coronary atherosclerosis, the lesions can be bypassed using an artery or vein graft. Frequently, the narrow segment can be dilated by inserting a balloon-tipped catheter into the diseased vessel through a peripheral artery and then inflating the balloon. Balloon inflation (angioplasty) can produce lasting dilation of a narrowed coronary artery, especially when a drug-eluting stent (which helps prevent restenosis) is inserted during angioplasty.

There are many drugs available for relieving angina pectoris, the chest pain associated with myocardial ischemia, in patients with coronary artery disease. These compounds include organic nitrates/nitrites, calcium channel antagonists, and β-adrenoceptor antagonists. Organic nitrates/nitrites are metabolized to nitric oxide (NO), which dilates the great veins to reduce venous return and cardiac work, thus reducing myocardial oxygen requirements. NO also dilates the coronary arteries to increase collateral flow. It is important to note that organic nitrates/nitrites do not interfere with coronary autoregulation. Calcium channel antagonists also cause vasodilation, particularly dilating the coronary vessels non-selectively. β-adrenoceptor antagonists reduce the heart rate to indirectly increase coronary flow and counteract the reflex tachycardia observed with organic nitrates/nitrites.
Prolongedreductionsincoronarybloodflow(myocardialischemia)maycriticallyandpermanentlyimpairthemechanicalandelectricalbehavioroftheheart.Diminishedcoronarybloodflowasaconsequenceofcoronaryarterydisease(usuallycoronaryatherosclerosis)isoneofthemostcommoncausesofseriouscardiacdisease.Theischemiamaybeglobal(affectsanentireventricle)orregional(affectssomefractionoftheventricle).TheimpairmentinmechanicalcontractionoftheaffectedmyocardiumisproducednotonlybythediminisheddeliveryofO2andmetabolicsubstratesbutalsobytheaccumulationofpotentiallyharmfulsubstances(e.g.,K+ ,lacticacid,H+)inthecardiactissues.Ifthereductionincoronaryflowtoanyregionoftheheartissufficientlysevereandprolonged,necrosisoftheaffectedcardiaccellsresults.
Myocardial hibernation describesthephenomenoninwhichcellularmetabolismisdownregulatedincellswhosefunctionisimpairedbyinadequatedeliveryofO2andnutrients.Myocardialhibernationoccursmainlyinpatientswithcoronaryarterydisease.Thecoronarybloodflowinsuchpatientsisdiminishedpersistentlyandsignificantly,andthemechanicalfunctionoftheheartisimpaired.Ifcoronarybloodflowisrestoredtonormalbybypasssurgeryorangioplasty,mechanicalfunctionreturnstonormal.
The O2 and nutrient requirements of the skin are relatively small. Unlike other body tissues, the supply of O2 and nutrients is not the chief factor in the regulation of cutaneous blood flow. The primary function of the cutaneous circulation is to maintain a constant body temperature. Thus the skin undergoes wide fluctuations in blood flow, depending on whether the body needs to lose or conserve heat. Changes in ambient and internal body temperature activate mechanisms responsible for alterations in skin blood flow.
Numeroussurgicalattemptshavebeenmadetoenhancethedevelopmentofcoronarycollateralvessels.However,thetechniquesuseddonotincreasethecollateralcirculationoverandabovethatproducedbycoronaryarterynarrowingalone.Whendiscreteocclusionsorseverenarrowingoccursincoronaryarteries,asincoronaryatherosclerosis,thelesionscanbebypassedwithanarteryoraveingraft.Frequently,thenarrowsegmentcanbedilatedbyinsertionofaballoon-tippedcatheterintothediseasedvesselviaaperipheralarteryandtheninflationoftheballoon.Distentionofthevesselbyballooninflation(angioplasty)canproducelastingdilationofanarrowed coronaryartery(Fig.17.36 ),particularlywhenadrug-elutingstent(thedrugshelppreventrestenosis)isinsertedduringangioplasty.
Manydrugsareavailableforuseinpatientswithcoronaryarterydiseasetorelieveanginapectoris,thechestpainassociatedwithmyocardialischemia.Thesecompoundsincludeorganicnitrates/nitrites,calciumchannelantagonists,andβ-adrenoceptorantagonists.Organicnitrates/nitritesaremetabolizedtoNO.NOdilatesthegreatveinstoreducevenousreturn(preload),therebyreducingcardiacwork(see )andmyocardialO2requirements.Inaddition,NOdilatesthecoronaryarteriestoincreasecollateralflow.Ofimportanceisthatorganicnitrates/nitritesdonotinterferewithcoronaryautoregulation.Calciumchannelantagonistsalsocausevasodilation;noneselectivelydilatesthecoronaryvessels.Theβ-adrenoceptorantagonistsreducetheheartratetoindirectlyincreasecoronaryflowandopposethereflextachycardiathathasbeenobservedwithorganicnitrates/nitrites.