Why do nitrates affect the preload of the right ventricle (RV) more than the left ventricle (LV)?

From the Guidelines

Nitrates affect the preload of the right ventricle more than the left ventricle primarily due to their predominant effect on venous capacitance vessels. When nitrates like nitroglycerin, isosorbide dinitrate, or isosorbide mononitrate are administered, they cause venodilation by releasing nitric oxide, which relaxes vascular smooth muscle 1. This venodilation increases the capacitance of the venous system, allowing more blood to pool in the peripheral veins. As a result, there is reduced venous return to the heart, which directly decreases right ventricular filling pressure and volume (preload). Since the right ventricle receives blood directly from the systemic venous circulation, it experiences this preload reduction first and most prominently. The left ventricle, which receives blood that has already passed through the pulmonary circulation, experiences a delayed and somewhat attenuated preload reduction. Additionally, the pulmonary vasculature can compensate for some of the reduced flow, further buffering the impact on left ventricular preload. This differential effect makes nitrates particularly useful in conditions like right ventricular infarction or right heart failure, where reducing right ventricular preload may be beneficial, though caution is needed as excessive preload reduction can compromise cardiac output.

Some key points to consider when using nitrates include:

• The dose and route of administration, with options including sublingual tablets, spray, transdermal, and intravenous 1
• The potential for reflex increases in heart rate and contractility, which can be mitigated with concurrent beta blocker administration 1
• The risk of systemic hypotension, particularly in patients with inferior wall myocardial infarction or suspected right ventricular infarction 1
• The importance of careful titration and monitoring to avoid excessive preload reduction and compromised cardiac output 1

Overall, the use of nitrates requires careful consideration of the potential benefits and risks, as well as close monitoring of the patient's response to therapy. By understanding the mechanisms by which nitrates affect the preload of the right and left ventricles, clinicians can optimize their use in a variety of clinical settings.

From the FDA Drug Label

The principal pharmacological action of Nitroglycerin Injection is relaxation of vascular smooth muscle and consequent dilatation of peripheral arteries and veins, especially the latter Dilatation of the veins promotes peripheral pooling of blood and decreases venous return to the heart, thereby reducing left ventricular end-diastolic pressure and pulmonary capillary wedge pressure (preload). Intravenous nitroglycerin reduced central venous pressure (CVP), right atrial pressure (RAP), pulmonary arterial pressure (PAP), pulmonary-capillary wedge pressure (PCWP), pulmonary vascular resistance (PVR), and systemic vascular resistance (SVR).

Nitrates affect the preload of the right ventricle more than the left ventricle because they cause dilatation of the veins, which promotes peripheral pooling of blood and decreases venous return to the heart. This reduction in venous return has a greater impact on the right ventricle, as it directly reduces the preload of the right ventricle by decreasing the amount of blood returning to the heart through the veins. The reduction in central venous pressure (CVP) and right atrial pressure (RAP) also supports this effect on the right ventricle 2.

From the Research

Mechanism of Nitrate Action

• Nitrates affect the preload of the right ventricle more than the left ventricle due to their mechanism of action, which involves the dilation of venous capacitance vessels 3, 4.
• This dilation leads to a decrease in venous pressure, resulting in a decrease in cardiac filling pressure 3.
• The decrease in cardiac filling pressure has a greater effect on the right ventricle, as it is more sensitive to changes in preload 4.

Effects on Left and Right Ventricles

• The left ventricle is able to maintain its stroke volume despite the decrease in preload, due to an improvement in left ventricular compliance 3.
• The right ventricle, on the other hand, experiences a greater decrease in preload, leading to a decrease in its stroke volume 4.
• The net effect of nitrate action is to translocate blood volume from the pulmonary circulation and left ventricle to the systemic vessels, which can lead to a decrease in right ventricular preload 4.

Clinical Implications

• Nitrates are effective in the treatment of acute heart failure, as they can reduce infarct size and improve long-term prognosis 5.
• However, nitrate therapy should be used with caution, as it can lead to tolerance and other side effects 5, 6.
• The clinical effects of nitrates on the central and peripheral circulations should be carefully considered when using these drugs in patients with cardiovascular disease 6.