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.